冠心病血栓形成相关标志物的初步研究
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摘要
第一部分冠心病血栓形成相关生化标志物研究
目的凝血、抗凝、纤溶及内皮功能异常与冠心病的发生、发展密切相关,已有研究发现,在心肌梗死发生之前可以检测到患者体内的高凝状态。单个研究较少涉及对多个血栓相关指标的探讨,因此,本研究的目的是评估多个血栓形成相关因子及一些其它危险因素对冠心病的影响。
方法冠心病组共56例,包括26例稳定型心绞痛(stable angina pectoris, SAP)及30例急性冠脉综合征(acute coronary syndrome, ACS)患者,均为2006年1月至7月在武汉协和医院心内科住院的患者;对照组54例,均为同期在该院其它科室住院的患者,排除了血栓栓塞性疾病、糖尿病、高血压病、恶性肿瘤、急慢性肝肾疾病及结缔组织病。病例组和对照组在年龄、性别及样本采集时间上均匹配。蛋白C(protein C, PC)、游离蛋白S(free protein S, FPS)、总蛋白S(total protein S, TPS)、凝血酶调节蛋白(thrombomodulin, TM)、活化凝血因子VII(activated factor VII, FVIIa)、凝血因子VII抗原(factor VII Antigen, FVIIag)、P选择素、组织型纤溶酶原激活剂(tissue-type plasminogen activator, tPA)及纤溶酶原激活剂抑制物-1(plasminogen activator inhibitor-1, PAI-1)的血浆水平均采用酶联免疫吸附法测定,组织因子活性(tissue factor activity, TFc)采用发色底物法测定,活化蛋白C(activated protein C, APC)比率、凝血酶原时间(prothrombin time, PT)、活化部分凝血活酶时间(activated partial thromboplastin time, APTT)、纤维蛋白原(fibrinogen, Fbg)、D二聚体(D-dimmer, DD)及凝血酶时间(thrombin time, TT)采用全自动血凝分析仪(Sysmex CA-7000,日本)检测。血脂水平由协和医院检验科统一测定(全自动生化分析仪7170A,Hitachi,日本)。
结果ACS组中TFc高于SAP组(P <0.05)和对照组(P <0.01);ACS组中FVIIag水平明显高于对照组(P<0.05);ACS组和SAP组中的FVIIa(P<0.01)、TM(P<0.05)及APC比率<2.4的阳性率(P<0.01)均明显高于对照组,APC比率均明显低于对照组(P<0.01);蛋白C、游离蛋白S、总蛋白S、P选择素、tPA、PAI-1血浆水平及APC抵抗阳性率在各组间均无统计学差异;Logistic回归分析显示,FVIIa及TFc的水平增高是冠心病的危险因素,高密度脂蛋白和APC比率增高是冠心病的保护性因素。
结论SAP和ACS患者均可出现外源性凝血途径的激活、对APC反应性的下降以及内皮功能的受损或活化;血浆中TFc增强可能预示了急性冠脉事件的发生;血浆FVIIa及TFc与冠心病的发病明显相关。
第二部分冠心病血栓形成相关蛋白标志物研究
目的利用表面增强激光解析/电离飞行时间质谱仪(SELDI-TOF-MS)及弱阳离子交换蛋白质芯片CM10检测急性心肌梗死患者和对照者血浆中蛋白质指纹图谱,筛选出不同组之间的差异蛋白质标志物并建立相应的诊断模型。
方法急性心肌梗死组77例,均为2006年1月～7月在武汉协和医院心内科住院患者,急性脑梗死组32例,为同期在该院神经内科住院患者,正常对照组60例。病例组和对照组在年龄、性别及样本采集时间上均匹配。将受试者血浆与CM10蛋白质芯片结合后,置入SELDI-TOF-MS系统进行蛋白质质谱测定,采用浙江大学肿瘤中心蛋白芯片数据分析系统对数据进行分析,找出差异蛋白质并建立相应诊断模型。
结果用SELDI-TOF-MS技术筛选出由5个有显著差异的蛋白质峰(质荷比分别为3321.6、16099.3、8058.7、15933.0和16286.7)组合构建的诊断模型,区分急性心肌梗死患者和正常人的诊断特异性和灵敏度分别为95%和88.3%;筛选出由17个蛋白质峰(质荷比分别为6682.6、6485.6、3321.6、16682.9、16297.7、7977.5、3424.7、4821.1、11748.7、4775.3、8977.3、9094.8、4361.4、11479.9、2941.1、11399.7和2462.3)组合构建的诊断模型,区分急性心肌梗死者和急性脑梗死者的诊断特异性和灵敏度均为100%。
结论SELDI-TOF-MS技术在急性心肌梗死的诊断上具有较高灵敏度和特异性,发现的蛋白质峰可能对急性心肌梗死的早期诊断具有一定价值。
第三部分MASA技术检测冠心病血栓形成相关基因变化
目的冠心病是一种多因素疾病,遗传因素也参与其发生和发展。本研究拟采用液相基因芯片技术(MASA)检测急性心肌梗死患者的7种基因多态性,并对阳性结果进行验证,探讨MASA技术检测基因变化的有效性。
方法一共有34例急性心肌梗死患者纳入研究,均为2006年1月～7月在武汉协和医院心内科住院患者。从血液中提取患者DNA并经PCR扩增,把针对7种基因改变(包括FV Leiden G/A突变、Fbg Beta -455 G/A突变、Fbg Beta -148 C/T突变、Fbg Beta 448 G/A突变、FVII -323 10bp插入突变、凝血酶原20210 G/A突变、MTHFR 677 C/T突变)的核酸探针以共价方式结合到特定荧光编码的微球上,把针对不同检测物的微球混合,加入PCR扩增产物杂交并标记荧光物质,利用Luminex 100?多功能流式点阵仪进行检测,采用Sanger双脱氧链中止法对阳性结果进行测序验证。
结果34例患者的MASA检测结果示,有19例存在基因变化,包括FV Leiden突变4例,MTHFR 677 C/T突变14例,纤维蛋白原β链448 G/A突变(Fbgβ448 G/A)5例,其中2例FV Leiden分别合并Fbgβ448 G/A突变和MTHFR677 C/T突变,2例MTHFR 677 C/T突变合并Fbgβ448 G/A突变。阳性结果经测序之后,证实一共15例患者存在基因变化,FV Leiden仅有1例突变,MTHFR 677 C/T突变12例,Fbgβ448 G/A突变4例,其中1例FV Leiden合并Fbgβ448 G/A突变,1例MTHFR 677 C/T突变合并Fbgβ448 G/A突变,MASA检测的阳性病例的总体正确率为73.9%。
结论液态基因芯片检测急性心肌梗死基因改变具有可行性,在基因研究中尚需对MASA技术进行进一步改进。
Part I Study on Biochemical Markers of Thrombosis in Coronary Heart Disease
Objective There are close relationships between disfunctions of coagulation, anticoagulation, fibrinolysis as well as endothelium and development of coronary heart disease. Some studies found that during pre-infarction phases, a hypercoagulable state may be detectable. Single research referring to multiple thrombosis factors is rare. Thus, the main objective of this study was to evaluate the effects of multiple thrombosis factors as well as some risk factors on coronary heart disease. Methods 56 patients with coronary artery disease (including 26 stable angina pectoris and 30 acute coronary syndromes) admitted to department of cardiology in Wuhan Union Hospital and 54 control patients excluded thromboembolic disease, diabetes mellitus, hypertension, malignant tumor, acute/chronic liver or kidney disease and connective tissue disease were enrolled from January to July 2006. Coronary artery disease group and control group were matched for age, sex and sampling time. Plasma levels of protein C, free protein S, total protein S, thrombomodulin, activated factor VII, factor VII Antigen, P-selectin, tissue-type plasminogen activator, plasminogen activator inhibitor-1 were measured by enzyme linked immunosorbent assay, activity of tissue factor was measured by chromogenic activity assay, and activated protein C ratio, prothrombin time, activated partial thromboplastin time, fibrinogen, D-dimmer and thrombin time were detected by full-automated coagulation analyzer (Sysmex CA-7000, Japan). Levels of blood lipids were assayed by Department of Laboratory of Union Hospital. Results The levels of tissue factor activity in patients with acute coronary syndromes were found to be significantly higher than those in controls (p<0.01) or in stable angina patients (p<0.05); the levels of FVIIag in ACS patients were significantly higher than those of controls; compared with controls, the plasma levels of FVIIa (P<0.01) and TM (P<0.05) as well as prevalences of APC ratio below 2.4 (P<0.01) in ACS and SAP groups were higher, however, APC ratios were lower (P<0.01). The result of binary logistic regression analysis showed that activated factor VII (OR 2.680, 95%CI 1.539-4.665) and tissue factor activity (OR 1.019, 95%CI 1.004-1.035) were risk factors, and high density lipoprotein (OR 0.008, 95%CI 0-0.478) and activated protein C ratio (OR 0.001, 95%CI 0-0.011) were protective factors for coronary heart disease. Conclusion There are activated extrinsic coagulation, lower response to activated protein C and damaged or activated endothelium function in SAP and ACS patients, plasma TFc may be a predictor for onset of ACS, plasma FVIIa and TFc are correlated with CHD.
Part II Study on Protein Markers of Thrombosis in Coronary Heart Disease
Objective To detect the plasma proteomic patterns in acute myocardial infarction (AMI) patients and controls, screen specific biomarkers and build diagnostic models by Surface-enhanced laser desorption/ionization time-of-flight mass spectrometer (SELDI-TOF-MS) and weak cation exchange protein chip (CM10). Methods 77 patients with acute myocardial infarction admitted to department of cardiology in Wuhan Union Hospital, 60 healthy controls and 32 patients with acute cerebral infarction (ACI) were enrolled from January to July 2006. Acute myocardial infarction group and control groups were matched for age, sex and sampling time. Protein chips combined with human plasma were placed in SELDI-TOF-MS for detecting protein profiling, analysis of the total experiment data was implemented by the Zhejiang University Cancer Institute-ProteinChip Data Analysis System (ZUCI-PDAS) for finding out discrepancy protein and building diagnostic models. Results A pattern composed five protein peaks (m/z: 3321.6, 16099.3, 8058.7, 15933.0 and 16286.7, respectively) with a specificity of 95% and a sensitivity of 88.3% was selected based on their collective contribution to the optimal separation between patients with AMI and healthy controls; A pattern composed seventeen protein peaks (m/z: 6682.6, 6485.6, 3321.6, 16682.9, 16297.7, 7977.5, 3424.7, 4821.1, 11748.7, 4775.3, 8977.3, 9094.8, 4361.4, 11479.9, 2941.1, 11399.7 and 2462.3, respectively) with a total accuracy of 100% was selected based on their collective contribution to the optimal separation between patients with AMI and patients with ACI. Conclusion Plasma proteomic profiling with SELDI-TOF-MS and ProteinChip technologies provides high sensitivity and specificity in discriminating patients with AMI and controls, and the discovered protein peaks might show great potential for early diagnosis of AMI.
Part III Study on Gene Markers of Thrombosis in Coronary Heart Disease by Multi-Analyte Suspension Array technology
Objective Coronary heart disease is caused by multiple factors, which also include genetic factors. The main objective of this study was to detect 7 gene polymorphisms in acute myocardial infarction (AMI) patients by liquid gene chip technology (MASA technology), and positive findings were verified, so as to find out validity of MASA technology in detecting gene variations. Methods 34 patients with acute myocardial infarction admitted to department of cardiology in Wuhan Union Hospital from January to July 2006 were enrolled in this trail. DNA was amplified by PCR technology after being extracted, nucleic acid probes of 7 gene variations (FV Leiden G/A mutation, Fbg Beta -455 G/A mutation, Fbg Beta -148 C/T mutation, Fbg Beta 448 G/A mutation, FVII -323 10bp deletion/insertion mutation, prothrombin 20210 G/A mutation and MTHFR 677 C/T mutation) were combined with microspheres (beads) by covalent bonds, the latter were coded with specified fluorescence, PCR products was added after various beads were mixed, the mixture was detected by Luminex 100? Multi-Analyte Suspension Array, finally, positive findings were verified by Sanger dideoxynucleotide chain termination. Results There were 19 patients with gene variations, including 4 patients with FV Leiden mutation, 14 patients with MTHFR 677 C/T mutation, 5 patients with fibrinogenβgene 448 G/A mutation, among them there were 1 patient with FV Leiden and Fbgβ448G/A mutation, 1 with FV Leiden and MTHFR677 C/T mutation, 2 with MTHFR677 C/T mutation and Fbgβ448G/A mutation, the total accuracy of MASA in positive findings was 73.9%. Conclusion Liquid gene chips technology is feasible in detecting gene variations in AMI patients, nevertheless, the MASA technology needs to improve.
目的凝血、抗凝、纤溶及内皮功能异常与冠心病的发生、发展密切相关,已有研究发现,在心肌梗死发生之前可以检测到患者体内的高凝状态。单个研究较少涉及对多个血栓相关指标的探讨,因此,本研究的目的是评估多个血栓形成相关因子及一些其它危险因素对冠心病的影响。
方法冠心病组共56例,包括26例稳定型心绞痛(stable angina pectoris, SAP)及30例急性冠脉综合征(acute coronary syndrome, ACS)患者,均为2006年1月至7月在武汉协和医院心内科住院的患者;对照组54例,均为同期在该院其它科室住院的患者,排除了血栓栓塞性疾病、糖尿病、高血压病、恶性肿瘤、急慢性肝肾疾病及结缔组织病。病例组和对照组在年龄、性别及样本采集时间上均匹配。蛋白C(protein C, PC)、游离蛋白S(free protein S, FPS)、总蛋白S(total protein S, TPS)、凝血酶调节蛋白(thrombomodulin, TM)、活化凝血因子VII(activated factor VII, FVIIa)、凝血因子VII抗原(factor VII Antigen, FVIIag)、P选择素、组织型纤溶酶原激活剂(tissue-type plasminogen activator, tPA)及纤溶酶原激活剂抑制物-1(plasminogen activator inhibitor-1, PAI-1)的血浆水平均采用酶联免疫吸附法测定,组织因子活性(tissue factor activity, TFc)采用发色底物法测定,活化蛋白C(activated protein C, APC)比率、凝血酶原时间(prothrombin time, PT)、活化部分凝血活酶时间(activated partial thromboplastin time, APTT)、纤维蛋白原(fibrinogen, Fbg)、D二聚体(D-dimmer, DD)及凝血酶时间(thrombin time, TT)采用全自动血凝分析仪(Sysmex CA-7000,日本)检测。血脂水平由协和医院检验科统一测定(全自动生化分析仪7170A,Hitachi,日本)。
结果ACS组中TFc高于SAP组(P <0.05)和对照组(P <0.01);ACS组中FVIIag水平明显高于对照组(P<0.05);ACS组和SAP组中的FVIIa(P<0.01)、TM(P<0.05)及APC比率<2.4的阳性率(P<0.01)均明显高于对照组,APC比率均明显低于对照组(P<0.01);蛋白C、游离蛋白S、总蛋白S、P选择素、tPA、PAI-1血浆水平及APC抵抗阳性率在各组间均无统计学差异;Logistic回归分析显示,FVIIa及TFc的水平增高是冠心病的危险因素,高密度脂蛋白和APC比率增高是冠心病的保护性因素。
结论SAP和ACS患者均可出现外源性凝血途径的激活、对APC反应性的下降以及内皮功能的受损或活化;血浆中TFc增强可能预示了急性冠脉事件的发生;血浆FVIIa及TFc与冠心病的发病明显相关。
第二部分冠心病血栓形成相关蛋白标志物研究
目的利用表面增强激光解析/电离飞行时间质谱仪(SELDI-TOF-MS)及弱阳离子交换蛋白质芯片CM10检测急性心肌梗死患者和对照者血浆中蛋白质指纹图谱,筛选出不同组之间的差异蛋白质标志物并建立相应的诊断模型。
方法急性心肌梗死组77例,均为2006年1月～7月在武汉协和医院心内科住院患者,急性脑梗死组32例,为同期在该院神经内科住院患者,正常对照组60例。病例组和对照组在年龄、性别及样本采集时间上均匹配。将受试者血浆与CM10蛋白质芯片结合后,置入SELDI-TOF-MS系统进行蛋白质质谱测定,采用浙江大学肿瘤中心蛋白芯片数据分析系统对数据进行分析,找出差异蛋白质并建立相应诊断模型。
结果用SELDI-TOF-MS技术筛选出由5个有显著差异的蛋白质峰(质荷比分别为3321.6、16099.3、8058.7、15933.0和16286.7)组合构建的诊断模型,区分急性心肌梗死患者和正常人的诊断特异性和灵敏度分别为95%和88.3%;筛选出由17个蛋白质峰(质荷比分别为6682.6、6485.6、3321.6、16682.9、16297.7、7977.5、3424.7、4821.1、11748.7、4775.3、8977.3、9094.8、4361.4、11479.9、2941.1、11399.7和2462.3)组合构建的诊断模型,区分急性心肌梗死者和急性脑梗死者的诊断特异性和灵敏度均为100%。
结论SELDI-TOF-MS技术在急性心肌梗死的诊断上具有较高灵敏度和特异性,发现的蛋白质峰可能对急性心肌梗死的早期诊断具有一定价值。
第三部分MASA技术检测冠心病血栓形成相关基因变化
目的冠心病是一种多因素疾病,遗传因素也参与其发生和发展。本研究拟采用液相基因芯片技术(MASA)检测急性心肌梗死患者的7种基因多态性,并对阳性结果进行验证,探讨MASA技术检测基因变化的有效性。
方法一共有34例急性心肌梗死患者纳入研究,均为2006年1月～7月在武汉协和医院心内科住院患者。从血液中提取患者DNA并经PCR扩增,把针对7种基因改变(包括FV Leiden G/A突变、Fbg Beta -455 G/A突变、Fbg Beta -148 C/T突变、Fbg Beta 448 G/A突变、FVII -323 10bp插入突变、凝血酶原20210 G/A突变、MTHFR 677 C/T突变)的核酸探针以共价方式结合到特定荧光编码的微球上,把针对不同检测物的微球混合,加入PCR扩增产物杂交并标记荧光物质,利用Luminex 100?多功能流式点阵仪进行检测,采用Sanger双脱氧链中止法对阳性结果进行测序验证。
结果34例患者的MASA检测结果示,有19例存在基因变化,包括FV Leiden突变4例,MTHFR 677 C/T突变14例,纤维蛋白原β链448 G/A突变(Fbgβ448 G/A)5例,其中2例FV Leiden分别合并Fbgβ448 G/A突变和MTHFR677 C/T突变,2例MTHFR 677 C/T突变合并Fbgβ448 G/A突变。阳性结果经测序之后,证实一共15例患者存在基因变化,FV Leiden仅有1例突变,MTHFR 677 C/T突变12例,Fbgβ448 G/A突变4例,其中1例FV Leiden合并Fbgβ448 G/A突变,1例MTHFR 677 C/T突变合并Fbgβ448 G/A突变,MASA检测的阳性病例的总体正确率为73.9%。
结论液态基因芯片检测急性心肌梗死基因改变具有可行性,在基因研究中尚需对MASA技术进行进一步改进。
Part I Study on Biochemical Markers of Thrombosis in Coronary Heart Disease
Objective There are close relationships between disfunctions of coagulation, anticoagulation, fibrinolysis as well as endothelium and development of coronary heart disease. Some studies found that during pre-infarction phases, a hypercoagulable state may be detectable. Single research referring to multiple thrombosis factors is rare. Thus, the main objective of this study was to evaluate the effects of multiple thrombosis factors as well as some risk factors on coronary heart disease. Methods 56 patients with coronary artery disease (including 26 stable angina pectoris and 30 acute coronary syndromes) admitted to department of cardiology in Wuhan Union Hospital and 54 control patients excluded thromboembolic disease, diabetes mellitus, hypertension, malignant tumor, acute/chronic liver or kidney disease and connective tissue disease were enrolled from January to July 2006. Coronary artery disease group and control group were matched for age, sex and sampling time. Plasma levels of protein C, free protein S, total protein S, thrombomodulin, activated factor VII, factor VII Antigen, P-selectin, tissue-type plasminogen activator, plasminogen activator inhibitor-1 were measured by enzyme linked immunosorbent assay, activity of tissue factor was measured by chromogenic activity assay, and activated protein C ratio, prothrombin time, activated partial thromboplastin time, fibrinogen, D-dimmer and thrombin time were detected by full-automated coagulation analyzer (Sysmex CA-7000, Japan). Levels of blood lipids were assayed by Department of Laboratory of Union Hospital. Results The levels of tissue factor activity in patients with acute coronary syndromes were found to be significantly higher than those in controls (p<0.01) or in stable angina patients (p<0.05); the levels of FVIIag in ACS patients were significantly higher than those of controls; compared with controls, the plasma levels of FVIIa (P<0.01) and TM (P<0.05) as well as prevalences of APC ratio below 2.4 (P<0.01) in ACS and SAP groups were higher, however, APC ratios were lower (P<0.01). The result of binary logistic regression analysis showed that activated factor VII (OR 2.680, 95%CI 1.539-4.665) and tissue factor activity (OR 1.019, 95%CI 1.004-1.035) were risk factors, and high density lipoprotein (OR 0.008, 95%CI 0-0.478) and activated protein C ratio (OR 0.001, 95%CI 0-0.011) were protective factors for coronary heart disease. Conclusion There are activated extrinsic coagulation, lower response to activated protein C and damaged or activated endothelium function in SAP and ACS patients, plasma TFc may be a predictor for onset of ACS, plasma FVIIa and TFc are correlated with CHD.
Part II Study on Protein Markers of Thrombosis in Coronary Heart Disease
Objective To detect the plasma proteomic patterns in acute myocardial infarction (AMI) patients and controls, screen specific biomarkers and build diagnostic models by Surface-enhanced laser desorption/ionization time-of-flight mass spectrometer (SELDI-TOF-MS) and weak cation exchange protein chip (CM10). Methods 77 patients with acute myocardial infarction admitted to department of cardiology in Wuhan Union Hospital, 60 healthy controls and 32 patients with acute cerebral infarction (ACI) were enrolled from January to July 2006. Acute myocardial infarction group and control groups were matched for age, sex and sampling time. Protein chips combined with human plasma were placed in SELDI-TOF-MS for detecting protein profiling, analysis of the total experiment data was implemented by the Zhejiang University Cancer Institute-ProteinChip Data Analysis System (ZUCI-PDAS) for finding out discrepancy protein and building diagnostic models. Results A pattern composed five protein peaks (m/z: 3321.6, 16099.3, 8058.7, 15933.0 and 16286.7, respectively) with a specificity of 95% and a sensitivity of 88.3% was selected based on their collective contribution to the optimal separation between patients with AMI and healthy controls; A pattern composed seventeen protein peaks (m/z: 6682.6, 6485.6, 3321.6, 16682.9, 16297.7, 7977.5, 3424.7, 4821.1, 11748.7, 4775.3, 8977.3, 9094.8, 4361.4, 11479.9, 2941.1, 11399.7 and 2462.3, respectively) with a total accuracy of 100% was selected based on their collective contribution to the optimal separation between patients with AMI and patients with ACI. Conclusion Plasma proteomic profiling with SELDI-TOF-MS and ProteinChip technologies provides high sensitivity and specificity in discriminating patients with AMI and controls, and the discovered protein peaks might show great potential for early diagnosis of AMI.
Part III Study on Gene Markers of Thrombosis in Coronary Heart Disease by Multi-Analyte Suspension Array technology
Objective Coronary heart disease is caused by multiple factors, which also include genetic factors. The main objective of this study was to detect 7 gene polymorphisms in acute myocardial infarction (AMI) patients by liquid gene chip technology (MASA technology), and positive findings were verified, so as to find out validity of MASA technology in detecting gene variations. Methods 34 patients with acute myocardial infarction admitted to department of cardiology in Wuhan Union Hospital from January to July 2006 were enrolled in this trail. DNA was amplified by PCR technology after being extracted, nucleic acid probes of 7 gene variations (FV Leiden G/A mutation, Fbg Beta -455 G/A mutation, Fbg Beta -148 C/T mutation, Fbg Beta 448 G/A mutation, FVII -323 10bp deletion/insertion mutation, prothrombin 20210 G/A mutation and MTHFR 677 C/T mutation) were combined with microspheres (beads) by covalent bonds, the latter were coded with specified fluorescence, PCR products was added after various beads were mixed, the mixture was detected by Luminex 100? Multi-Analyte Suspension Array, finally, positive findings were verified by Sanger dideoxynucleotide chain termination. Results There were 19 patients with gene variations, including 4 patients with FV Leiden mutation, 14 patients with MTHFR 677 C/T mutation, 5 patients with fibrinogenβgene 448 G/A mutation, among them there were 1 patient with FV Leiden and Fbgβ448G/A mutation, 1 with FV Leiden and MTHFR677 C/T mutation, 2 with MTHFR677 C/T mutation and Fbgβ448G/A mutation, the total accuracy of MASA in positive findings was 73.9%. Conclusion Liquid gene chips technology is feasible in detecting gene variations in AMI patients, nevertheless, the MASA technology needs to improve.
引文
1.胡大一,孙艺红.冠心病药物治疗的最新进展和展望.中国实用内科杂志,2006,26:88-91.
2. Fareed J, Hoppensteadt DA, Leya F, et al. Useful laboratory tests for studying thrombogenesis in acute cardiac syndromes. Clin Chem,1998,44: 1845-1853.
3. Lisowski P, Malyszko J, Lisowska A, et al. Role of the hemostatic system in pathogenesis of atherosclerosis as the main etiology of coronary ischemia. Pol Merkur Lekarski,2004,16: 465-467.
4. Amiral J, Fareed J. Thromboembolic disease: biochemical mechanisms and new possibilities of biological diagnosis. Semin Thromb Hemost,1996,22:41-48.
5. Broze G, Miletich JP. Characterization of the inhibition of tissue factor in serum. Blood,1987,69:150-155.
6. Broze G, Warren J, Novotny LA, et al. The lipoprotein associated coagulation inhibitor that inhibits the factor VIIa-tissue factor complex, also inhibits factors Xa: insight into its possible mechanism of action. Blood,1988,71:335-343.
7. Bauer KA, Rosenberg RD. The pathophysiology of the prothrombotic state in humans: insight gained from studies using analytes of hemostatic system activation. Blood,1987,70: 343-350.
8. Messmore HL, Walenga JM, Fareed J. Molecular analytes of platelet activation. Semin Thromb Hemost,1984,10:264-269.
9. Aurousseau MH, Amiral J, Boffa MC. Level of plasma thrombomodulin in neonates and children. Thromb Hemost,1991,65:12-32.
10. Stephens CJM. The antiphospholipid syndrome. Clinical correlations, cutaneous features, mechanism of thrombosis and treatment of patients with the lupus anticoagulant and anticardiolinpin antibodies. Br J Dermatol, 1991,125:199-210.
11. Donner MG, Klein GK, Mathes PB, et al. Plasma total homocycteine levels in patients with early-onset coronary heart disease and a low cardiovascular risk profile. Metab Clin Exp,1998,47: 273-279.
12. Kohler HP, Carter AM, Stickland MH, et al. Level of activated FXII in survivors of myocardial infarction-association with circulating risk factors and extent of coronary artery disease. Thromb Hemost,1998,79: 14-18.
13. Steffel J, Luscher TF, Tanner FC. Tissue factor in cardiovascular diseases: molecular mechanisms and clinical implications. Circulation, 2006, 113: 722-731.
14. Tilley R, Mackman N. Tissue factor in hemostasis and thrombosis. Semin Thromb Hemost,2006,32: 5-10.
15. Mallat Z, Tedgui A. Current perspective on the role of apoptosis in atherothrombotic disease. Circ Res,2001,88: 998-1003.
16. Corti R, Fuster V,Badimon JJ. Pathogenetic concepts of acute coronary syndromes. J Am Coll Cardiol, 2003, 41:7-14.
17. Porreca E, Di Febbo C, di Castelnuovo A, et al. Association of factor VII levels with inflammatory parameters in hypercholesterolemic patients. Atherosclerosis, 2002,165: 159-166.
18. Heinrich J, Balleisen L, Schulte H, et al. Fibrinogen and factor VII in the prediction of coronary risk. Results from the PROCAM Study in healthy men. Arterioscler Thromb,1994,14:54-59.
19. 19 De Stavola BL and Meade TW. Long-term effects of hemostatic variables on fatal coronary heart disease: 30-year results from the first prospective Northwick Park Heart Study (NPHS-I). J Thromb Haemost, 2007,5:461-471.
20. Junker R, Heinrich J, Schulte H, et al. Coagulation factor VII and the risk of coronary heart disease in healthy men. Arterioscler Thromb Vasc Biol, 1997,17:1539-1544.
21. Folsom AR, Wu KK, Rosamond WD, et al. Prospective study of hemostatic factors and incidence of coronary heart disease. Circulation,1997,96: 1102-1108.
22. Tracy RP, Arnold AM, Ettinger W, et al. The relationship of fibrinogen and factor VII and VIII to incident cardiovascular disease and death in the elderly. Results from the cardiovascular health study. Arterioscler Thromb Vasc Biol,1999,19: 1776-1783.
23. Cooper JA, Miller GJ, Bauer KA, et al. Comparison of novel hemostatic factors and conventional risk factors for prediction of coronary heart disease. Circulation, 2000, 102:2816-2822.
24. Woodhouse PR, Khaw KT, Plummer M, et al. Seasonal variations of plasma fibrinogen and factor VII activity in the elderly: winter infections and death from cardiovascular disease. Lancet,1994,343: 435-439.
25. Ridker PM. Fibrinolytic and inflammatory markers for arterial occlusion: the evolving epidemiology of thrombosis and haemostasis. Thromb Haemost, 1997, 78: 53-59.
26. Laffan MA. Activated protein C resistance and myocardial infarction. Heart, 1998,80: 319-321.
27. Kabukcu S, Keskin N, Kesdin A, et al. The frequency of factor V Leiden and concomitance of factor V Leiden with prothrombin G20210A mutation and methylene tetrahydrofolate reductase C677T gene mutation in healthy population of Denizli, Aegean region of Turkey. Clin Appl Thromb Hemost, 2007, 13: 166-171.
28.马爱华,李牧尧,康福信,等.新疆地区汉族和哈萨克族正常人群中FV Leiden突变的初步调查.中华血液学杂志,1999,20: 267.
29. Wu J, Gu J, Xu J, et a1.Factor V Leiden mutation in one family of Chinese origin. Chin Med J, 2001, 114: 379-381.
30.罗佳滨,关月,马洪星,等.凝血因子V基因突变1691A在不同种族人群中的分布.中华医学遗传学杂志,1996,13: 219-220.
31. Rosendorff A, Dorfman DM. Activated protein C resistance and factor V Leiden: a review. Arch Pathol Lab Med, 2007, 131: 866-871.
32. Sakata T, Kario K, Katayama Y, et al. Clinical significance of activated protein C resistance as a potential marker for hypercoagulable state. Thromb Res, 1996, 82: 235-244.
33. Avellone G, Di Garbo V, Di Raimondo D, et al. Evaluation of resistance to activated protein C in myocardial infarction patients. Minerva Cardioangiol,2001,49: 363-368.
34. Makris TK, Krespi PG, Hatzizacharias AN, et al. Resistance to activated protein C and FV leiden mutation in patients with a history of acute myocardial infarction or primary hypertension. Am J Hypertens, 2000,13: 61-65.
35. Hayashi K, Sone T, Kondoh J, et al. Prevalence of activated protein C resistance in acute myocardial infarction in Japan. Jpn Heart J, 1997, 38: 769–778.
36. Prohaska W, Mannebach H, Schmidt M, et al. Evidence against heterozygous coagulation factor V 1691 G-->A mutation with resistance to activated protein C being a risk factor for coronary artery disease and myocardial infarction. J Mol Med,1995,73:521-524.
37.郑延松,郑秋甫.活化蛋白C抵抗现象与血栓性疾病的关系.国外医学心血管疾病分册,2004,31: 87-89.
38. Salomaa V, Matei C, Aleksic N, et al. Soluble thrombomodulin as a predictor of incident coronary heart disease and symptomless carotid artery atherosclerosis in the Atherosclerosis Risk in Communities (ARIC) Study: a case-cohort study. Lancet, 1999,353:1729-1734.
39. Blann AD, Amiral J, McCollum CN. Prognostic value of increased soluble thrombomodulin and increased soluble E-selectin in ischaemic heart disease. Eur J Haematol,1997, 59:115-120.
40. Wu KK. Soluble thrombomodulin and coronary heart disease . Curr Opin Lipidol, 2003, 14: 373-375.
41. Olivot JM, Labreuche J, Aiach M, et al. Soluble thrombomodulin and brain infarction: case-control and prospective study. Stroke,2004,35: 1946-1951.
1.杨旭玲,裴晓冬.心肌肌钙蛋白T在急性冠脉综合症诊断中的意义.中国实验诊断学,2007,11:23-24.
2. Alpert JS, Thygesen K, Antman E, et al. Myocardial infarction redefined-A consensus document of the European Society of Cardiology/American college of Cardiology Committee for the redefinition of myocardial infarction. J Am Coll Cardial,2000,36: 959-969.
3.陈绍良.急性心肌梗死细胞再生治疗进展.临床内科杂志,2007,24:5-7.
4. Rodland KD. Proteomics and cancer diagnosis: the potential of mass spectrometry. Clinical Biochemistry, 2004, 37: 579-583.
5. Poon TC, Yip TT, Chan AT, et al. Comprehensive proteomic profiling identifies serum proteomic signatures for detection of hepatocellular carcinoma and its subtypes. Clin Chem, 2003, 49: 752–760.
6. Grus FH, Podust VN, Bruns K, et al.SELDI-TOF-MS proteinchip array profiling of tears from patients with dry eye. Invest Ophthalmol Vis Sci, 2005, 46: 863-876.
7.褚福亮,王福生.蛋白质谱分析方法特点及其在蛋白组学研究领域中的应用.世界华人消化杂志,2002,10:1431-1435.
8. Liu Y. Active learning with support vector machine applied to gene expression data for cancer classification. J Chem Inf Comput Sci, 2004, 44: 1936-1941.
9. Hutchens TW, Yip TT. New desorption strategies for the mass spectrometric analysis of macromolecules. Rapid Comm Mass Spectrum, 1993,7:576-580.
10. Smith RD, Anderson GA,Lipton MS, et al. An accurate mass tag strategy for quantitative and high-throughput proteme measurements. Proteomics, 2002, 2:513-523.
11. Foret F, Preisler J. Liquid phase interfacing and miniaturization in matrix-assisted laser desorption/ionixation mass spectrometry. Proteomics, 2002, 2: 360-370.
12.罗治文.质谱技术研究进展.国外医学生物医学工程分册.2005,28:134-137.
13. Wright GL, Cazares LH, Leung SM. ProteinChip surface enhanced laser desorption/ionization (SELDI) mass spectromatry: a novel protein biochip technologyfor detection of biomarker in complex protein mixtures. Prostate Cancer Prostatic Dis, 2000,2:264-276.
14. Amiral J, Fareed J. Thromboembolic diseases: biochemical mechanisms and new possibilities of biological diagnosis. Semin Thromb Hemost, 1996, 22: 41-48.
15.胡跃,张苏展,余捷凯等.乳腺癌患者血清蛋白质指纹图谱检测及其临床意义.中华检验医学杂志,2004,27: 646-648.
16. Baggerly KA, Morris JS, Coombes KR. Reproducibility of SELDI-TOF protein patterns in serum:comparing datasets from different experiments. Bioinformatics, 2004,20: 777–785.
17. Seibert V, Ebert MP, Buschmann T. Advances in clinical cancer proteomics: SELDI-TOF-mass spectrometry and biomarker discovery. Brief Funct Genomic Proteomic,2005,4:16-26.
18. Liotta LA, Lowenthal M, Mehta A, et al. Importance of communication between producers and consumers of publicly available experimental data. J Natl Cancer Inst,2005,97: 310-314.
19. Banks RE, Stanley AJ, Cairns DA, et al. Influences of blood sample processing on low-molecular-weight proteome identified by surface-enhanced laser desorption/ ionization mass spectrometry. Clin Chem, 2005, 51: 1637-1649.
20. Byvatov E, Schneider G. Support vector machine applications in bioinformatics. Appl Bioinformatics, 2003, 2: 67-77.
21. Jorissen RN, Gilson MK. Virtual screening of molecular databases using a support vector machine. J Chem Inf Model, 2005, 45: 549-561.
1.王晓玲,顾东风.冠心病遗传因素的研究进展.中华医学遗传学杂志,2000,17:452-454.
2.谭光波,毛以林,袁肇凯.冠心病基因多态性研究进展.中西医结合心脑血管病杂志,2004,2:98-100.
3. Yoneya K, Okamoto H, Kitabatake A. Genetic polymorphisms as risk factors for coronary artery disease. Nippon Rinsho, 1998,56:2509-2514.
4. Taylor G R and Deeble J. Enzymatic methods for mutation scanning. Genet Anal,1999,14:181–186.
5. Fodde R and Losekoot M. Mutation detection by denaturing gradient gel electrophoresis (DGGE). Hum Mutat,1994,3:83–94.
6. Lancaster JM, Berchuck A, Futreal P A, et al. Dideoxy fingerprinting assay for BRCA1 mutation analysis. Mol Carcinog.1997,19: 176–179.
7. Markoff A, Savov A, Vladimirov V, et al. Optimization of single-strand conformation polymorphism analysis in the presence of polyethylene glycol. Clin Chem, 1997,43:30–33.
8. Hedberg JJ, Backlund M, Stromberg P, et al. Functional polymorphism in the alcohol dehydrogenase 3 (ADH3) promoter. Pharmacogenetics, 2001,11: 815–824.
9. Markoff A, Sormbroen H, Bogdanova N, et al. Comparison of conformation-sensitive gel electrophoresis and single-strand conformation polymorphism analysis for detection of mutations in the BRCA1 gene using optimized conformation analysis protocols. Eur J Hum Genet, 1998, 6: 145–150.
10. Ezzeldin H, Okamoto Y, Johnson MR, et al. A High-Throughput Denaturing High-Performance Liquid Chromatography Method for the Identification of Variant Alleles Associated with Dihydropyrimidine Dehydrogenase Deficiency. Anal Biochem, 2002, 306:63-73.
11. Taylor JD, Briley D, Nguyen Q, et al. Flow cytometric platform for high-throughput single nucleotide polymorphism analysis. Biotechniques,2001,30:661-666, 668-669.
12.张华宁,高雪芹,韩金祥.多色微球液相芯片技术的原理及其应用.山东医药,2006,46:71-72.
13.何英,陆学东.液相芯片技术及其临床应用.国际检验医学杂志,2006,27:1107-1111.
14.牟颖,金钦汉.荧光编码微球-流式细胞和生化分析技术及其最新发展.2003,1:31-36.
15.王蕾,吴英松,李明.液相芯片分析技术及其应用简介.热带医学杂志,2005,5:562-564.
16. Biagini RE, Sammons DL, Smith JP. Comparison of a multiplexed fluorescent covalent microsphere immunoassay and an enzyme-linked immunosorbent assay for measurement of human immunoglobulin G antibodies to anthrax toxins. Clin Diagn Lab Immunol, 2004,11:50-55.
17. Nata M, Hashiyada M. Analysis of the single nucleotide polymorphism of mitochondrial DNA by liquid bead array technology. Int Congr Ser, 2004, 1261:369-371.
18. Deregt D, Gilbert SA, Dudas S, et al.A multiplex DNA suspension microarray for simultaneous detection and differentiation of classical swine fever virus and other pestiviruses. J Virol Methods, 2006,136:17-23.
19. Hadd AG, Laosinchai-Wolf W, Novak CR. Microsphere bead arrays and sequence validation of 5/7/9T genotypes for multiplex screening of cystic fibrosis polymorphisms. J of Mol Diagnos, 2004,6:348-355.
20. Bellisario R ,Colinas RJ , Pass KA. Simultaneous measurement of thyroxine and thyrotropin from newborn dried blood-spot specimens using a multiplexed fluorescent microsphere immunoassay. Clin Chem ,2000 ,46 :1422-1424.
21. Dahlback B, Carlsson M, Svensson PJ.Familial thrombophilia due to a previously unrecognized mechanism characterized by poor anticoagulant response to activated protein C: prediction of a cofactor to activated protein C. Proc Natl Acad Sci USA, 1993, 90:1004-1008.
22. Bertina RM, Koeleman BP, Koster T, et a1.Mutation in blood coagulation factor Vassociated with resistance to activated protein C.Nature, 1994, 369: 64-67.
23. Khare A, Ghosh K, Shetty S, et al. Combination of thrombophilia markers in acute myocardial infarction of the young. Indian J Med Sci, 2004, 58:381-388.
24. Tanis BC, Bloemenkamp DG, van den Bosch MA, et al. Prothrombotic coagulation defects and cardiovascular risk factors in young women with acute myocardial infarction. Br J Haematol, 2003, 122:471-478.
25.马爱华,李牧尧,康福信,等.新疆地区汉族和哈萨克族正常人群中FV Leiden突变的初步调查.中华血液学杂志,1999,20: 267.
26. Wu J, Gu J, Xu J, et a1.Factor V Leiden mutation in one family of Chinese origin.Chin Med J, 2001, 114: 379-381.
27.罗佳滨,关月,马洪星,等.凝血因子V基因突变1691A在不同种族人群中的分布.中华医学遗传学杂志,1996,13: 219-220.
28. Burzotta F, Paciaroni K, De Stefano V, et al. G20210A prothrombin gene polymorphism and coronary ischaemic syndromes: a phenotype-specific meta-analysis of 12 034 subjects. Heart, 2004,90:82-86.
29. Lane DA, Grant PJ. Role of hemostatic gene polymorphism in venous and arterial thrombotic disease. Blood, 2000, 95:1517-1532.
30.陶蓉,于金德,陆林等.凝血因子VII活性与多态性关系的研究.中华心血管病杂志,2000,28:27-29.
31. Campo G, Valgimigli M, Ferraresi P,et al. Tissue factor and coagulation factor VII levels during acute myocardial infarction: association with genotype and adverse events. Arterioscler Thromb Vasc Biol, 2006, 26:2800-2806.
32. Rothenbacher D,Fischer HG,Hoffmeister A,et al. Homocysteine and methylenetetrahydrofolate reductase genotype:association with resk of coronary heart disease and relation to inflammatory,hemostatic,and lipid parameters. Atherosclerosis, 2002,162:193-200.
33.祝鸿喜,马向红,黄体钢等.MTHFR基因多态性与冠心病的关系.实用心脑肺血管病杂志,2007,15:569-572.
1. REVAK SD, COCHRANE CG, JOHNSTON AR, et al. Structural changes accompanying enzymatic activation of human Hageman factor. J Clin Invest. 1974, 54: 619-627.
2. KANAJI T, OKAMURA T, OSAKI K, et al. A common genetic polymorphism (46 C to T substitution) in the 5'-untranslated region of the coagulation factor XII gene is associated with low translation efficiency and decrease in plasma factor XII level. Blood. 1998, 91: 2010-2014.
3. COOL DE, EDGELL CJ, LOUIE GV, et al. Characterization of human blood coagulation factor XII cDNA. Prediction of the primary structure of factor XII and the tertiary structure of beta-factor XIIa. J Biol Chem. 1985, 260:13666-13676.
4.周运恒,王鸿利.凝血因子XII与纤维蛋白溶解的关系.医学综述, 2002, 8(4): 223-224.
5. ROYLE NJ, NIGLI M, Cool D, et al. Structural gene encoding human factor XII is located at 5q33-qter. Somat Cell Mol Genet. 1988, 14: 217-221.
6. COOL DE, MACGILLIVRAY RT. Characterization of the human blood coagulation factor XII gene. Intron/exon gene organization and analysis of the 5'-flanking region. J Biol Chem. 1987, 262: 13662-13673.
7. ENDLER G, EXNER M, MANNHALTER C, et al. A common C-->T polymorphism at nt 46 in the promoter region of coagulation factor XII is associated with decreased factor XII activity. Thromb Res. 2001, 101: 255-260.
8. KONDO S, TOKUNAGA F, KAWANO S, et al. Factor XII Tenri, a novel cross-reacting material negative factor XII deficiency, occurs through a proteasome-mediated degradation. Blood. 1999, 93: 4300-4308.
9. HOFFERBERT S, MULLER J, KOSTERING H, et al. A novel 5'-upstream mutation in the factor XII gene is associated with a TaqI restriction site in an Alu repeat in factor XII-deficient patients. Hum Genet. 1996, 97: 838-841.
10. SCHLOESSER M, HOFFERBERT S, BARTZ U, et al. The novel acceptor splice site mutation 11396(G-->A) in the factor XII gene causes a truncated transcript incross-reacting material negative patients. Hum Mol Genet. 1995, 4: 1235-1237.
11. KANAJI T, KANAJI S, OSAKI K, et al. Identification and characterization of two novel mutations (Q421 K and R123P) in congenital factor XII deficiency. Thromb Haemost. 2001, 86: 1409-1415.
12. KANAJI T, OKAMURA T, OSAKI K, et al. A common genetic polymorphism (46 C to T substitution) in the 5'-untranslated region of the coagulation factor XII gene is associated with low translation efficiency and decrease in plasma factor XII level. Blood. 1998, 91: 2010-2014.
13. ISHII K, OGUCHI S, MURATA M, et al. Activated factor XII levels are dependent on factor XII 46C/T genotypes and factor XII zymogen levels, and are associated with vascular risk factors in patients and healthy subjects. Blood Coagul Fibrinolysis. 2000, 11: 277-284.
14. SANTAMARIA A, MATEO J, TIRADO I, et al. Homozygosity of the T allele of the 46 C->T polymorphism in the F12 gene is a risk factor for ischemic stroke in the Spanish population. Stroke. 2004, 35: 1795-1799.
15. OGUCHI S, ITO D, MURATA M, et al. Genotype distribution of the 46C/T polymorphism of coagulation factor XII in the Japanese population: absence of its association with ischemic cerebrovascular disease. Thromb Haemost. 2000, 83: 178-179.
16. ZITO F, LOWE GD, RUMLEY A, et al. WOSCOPS Study Group West of Scotland Coronary Prevention Study. Association of the factor XII 46C>T polymorphism with risk of coronary heart disease (CHD) in the WOSCOPS study. Atherosclerosis. 2002, 165: 153-158.
17. ZITO F, DRUMMOND F, BUJAC SR, et al. Epidemiological and genetic associations of activated factor XII concentration with factor VII activity, fibrinopeptide A concentration, and risk of coronary heart disease in men. Circulation. 2000, 102: 2058-2062.
18. ENDLER G, MANNHALTER C, SUNDER-PLASSMANN H, et al. Homozygosity for the C-->T polymorphism at nucleotide 46 in the 5' untranslated region of the factor XII gene protects from development of acute coronary syndrome. Br J Haematol.2001, 115: 1007-1009.
19. KOHLER HP, FUTERS TS, GRANT PJ. FXII (46C-->T) polymorphism and in vivo generation of FXII activity--gene frequencies and relationship in patients with coronary artery disease. Thromb Haemost. 1999, 81: 745-747.
20. TIRADO I, SORIA JM, MATEO J, et al. Association after linkage analysis indicates that homozygosity for the 46C-->T polymorphism in the F12 gene is a genetic risk factor for venous thrombosis. Thromb Haemost. 2004, 91: 899-904.
21. ORTH M, WESTPHAL S, DIERKES J, et al. Rapid factor XII (46C-->T) genotyping by fluorescence resonance energy transfer in patients with coronary artery disease or thrombophilia. Clin Chem. 2001, 47: 1117-1119.
1. Bertina RM, Koeleman BP, Koster T, et a1.Mutation in blood coagulation factor V associated with resistance to activated protein C.Nature, 1994, 369: 64-67.
2. Nicolaes GA, Tans G, Thomassen MC, et at. Peptide bond cleavages and loss of functiona1 activity during inactivation of factor Va and factor VaR506Q by activated protein C.J Bio1 Chem, 1995, 270: 21158-21166.
3. Chan WP, Lee CK, Kwong YL, et al. A Novel mutation of Arg306 of factor V gene in Hong Kong Chinese. Blood, 1998, 91:1135-1139.
4. Williamson D, Brown K, Luddington R, et a1.Factor V Cambridge: a new mutation(Arg306→Thr) associated with resistance to activated protein C.Blood, 1998, 91: l140-l144.
5. Kabukcu S, Keskin N, Kesdin A, et al. The frequency of factor V Leiden and concomitance of factor V Leiden with prothrombin G20210A mutation and methylene tetrahydrofolate reductase C677T gene mutation in healthy population of Denizli, Aegean region of Turkey. Clin Appl Thromb Hemost, 2007, 13: 166-171.
6.马爱华,李牧尧,康福信,等.新疆地区汉族和哈萨克族正常人群中FV Leiden突变的初步调查.中华血液学杂志,1999,20: 267.
7. Wu J, Gu J, Xu J, et a1.Factor V Leiden mutation in one family of Chinese origin.Chin Med J, 2001, 114: 379-381.
8.罗佳滨,关月,马洪星,等.凝血因子V基因突变1691A在不同种族人群中的分布.中华医学遗传学杂志,1996,13: 219-220.
9. Khare A, Ghosh K, Shetty S, et al. Combination of thrombophilia markers in acute myocardial infarction of the young. Indian J Med Sci, 2004, 58:381-388.
10. Tanis BC, Bloemenkamp DG, van den Bosch MA, et al. Prothrombotic coagulation defects and cardiovascular risk factors in young women with acute myocardial infarction. Br J Haematol, 2003, 122:471-478.
11. Doix S, Mahrousseh M, Jolak M, et al. Factor V Leiden and myocardial infarction: acase, review of the literature with a meta-analysis. Ann Cardiol Angeiol (Paris), 2003,52:143-149.
12. D?nmez Y, Kanadasi M, Tanriverdi K, et al. Prothrombin 20210GA and factor V Leiden mutations in patients less than 55 years old with myocardial infarction. Jpn Heart J, 2004, 45:505-512.
13. Yanqing H, Fangping C, Qinzhi X, et al. No association between thrombosis and factor V gene polymorphisms in Chinese Han population. Thromb Haemost, 2003, 89:446-451.
14. Baykan M, Celik S, U?ar F, et al. Effects of factor V Leiden mutations on prognosis in patients with acute myocardial infarction. Anadolu Kardiyol Derg, 2001,1:242-245; AXIV.
15. Gowda MS, Zucker ML, Vacek JL, et al. Incidence of factor V Leiden in patients with acute myocardial infarction. J Thromb Thrombolysis, 2000, 9:43-45.
16. Lane DA, Grant PJ. Role of hemostatic gene polymorphism in venous and arterial thrombotic disease. Blood, 2000, 95:1517-1532.
17. de Maat MP, Kastelein JJ, Jukema JW, et al. -455G/A polymorphism of the beta-fibrinogen gene is associated with the progression of coronary atherosclerosis in symptomatic men: proposed role for an acute-phase reaction pattern of fibrinogen. REGRESS group. Arterioscler Thromb Vasc Biol, 1998,18:265-271.
18.马会利,陈纪林,冯军等.年轻心肌梗死患者纤维蛋白原基因βG455A多态性研究.中华心血管病杂志,2002,30:74-77.
19. Zito F, Di Castelnuovo A, Amore C, et al. Bcl I polymorphism in the fibrinogen beta-chain gene is associated with the risk of familial myocardial infarction by increasing plasma fibrinogen levels. A case-control study in a sample of GISSI-2 patients. Arterioscler Thromb Vasc Biol, 1997, 17:3489-3494.
20.王晓明,张桂茹,马学玲等.缺血性心脏病与β-纤维蛋白原基因bcl-I多态性和血浆纤维蛋白原水平的关系.吉林大学学报(医学版), 2005,31:791-794.
21. Girelli D, Russo C, Ferraresi P, et al. Polymorphisms in the factor VII gene and the risk of myocardial infarction in patients with coronary artery disease. N Eng J Med, 2000,343:774-780.
22. Heywood DM, Ossei-Gerning N, Grant PJ. Association of factor VII:C levels with environmental and genetic factors in patients with ischaemic heart disease and coronary atheroma characterised by angiography. Thromb Haemost, 1996, 76:161-165.
23. Campo G, Valgimigli M, Ferraresi P,et al. Tissue factor and coagulation factor VII levels during acute myocardial infarction: association with genotype and adverse events. Arterioscler Thromb Vasc Biol, 2006, 26:2800-2806.
24. Carew JA, Basso F, Miller GJ, et al. A functional haplotype in the 5' flanking region of the factor VII gene is associated with an increased risk of coronary heart disease. J Thromb Haemost, 2003, 1:2179-2185.
25. Batalla A, Alvarez R, Reguero JR, et al. Lack of association between polymorphisms of the coagulation factor VII and myocardial infarction in middle-aged Spanish men. Int J Cardiol, 2001, 80:209-212.
26. Feng YJ, Draghi A, Linfert DR, et al. Polymorphisms in the genes for coagulation factors II, V, and VII in patients with ischemic heart disease. Arch Pathol Lab Med, 1999, 123:1230-5120.
27. Ariens RA, Philipou H, Nagaswami C, et al. The factor XIII Val34Leu polymorphism accelerates theombin activation of factor XIII and affects cross-linked fibrin structure. Blood, 2000, 96:988-995.
28. Kakko S, Elo T, Tapanainen JM, et al. Polymorphisms of genes affecting thrombosis and risk of myocardial infarction. Eur J Clin Invest, 2002, 32:643-648.
29. Kohler HP, Stickland MH, Ossei-Gerning N, et al. Association of a common polymorphism in the factor XIII gene with myocardial infarction. Thromb Haemost, 1998,79:8-13.
30. Shafey M, Anderson JL, Scarvelis D, et al. Factor XIII Val34Leu variant and the risk of myocardial infarction: a meta-analysis. Thromb Haemost, 2007,97:635-641.
31. Burzotta F, Paciaroni K, De Stefano V, et al. G20210A prothrombin gene polymorphism and coronary ischaemic syndromes: a phenotype-specific meta- analysis of 12 034 subjects. Heart, 2004,90:82-86.
32. Burzotta F, Paciaroni K, De Stefano V, et al. Increased prevalence of the G20210Aprothrombin gene variant in acute coronary syndromes without metabolic or acquired risk factors or with limited extent of disease. Eur Heart J, 2002, 23:26-30.
33. Croft SA, Daly ME, Steeds RP, et al. The prothrombin 20210A allele and its association with myocardial infarction. Thromb Haemost, 1999, 81:861-864.
34. Eikelboom JW, Baker RI, Parsons R, et al. No association between the 20210 G/A prothrombin gene mutation and premature coronary artery disease. Thromb Haemost, 1998,80:878-880.
35.唐雪元,陈方平,解勤之等.急性心肌梗死患者凝血酶原基因G20210A变异频度分析.中国现代医学杂志.2002,12:33-37.
36.钱高潮,李稻,王鸿利.血栓调节蛋白基因变异的研究进展.国外医学输血及血液学分册,2002,25:193-195.
37. Chao TH, Li YH, Chen JH, et al. Relation of thrombomodulin gene polymorphisms to acute myocardial infarction in patients 38. Ranjith N, Pegoraro RJ, Rom L. Haemostatic gene polymorphisms in young indian asian subjects with acute myocardial infarction. Med Sci Monit, 2003, 9:CR417-421.
39. Li YH, Chen JH, Tsai WC, et al. Synergistic effect of thrombomodulin promoter -33G/A polymorphism and smoking on the onset of acute myocardial infarction. Thromb Haemost, 2002,87:86-91.
40. Norlund L, Holm J, Z?ller B, et al. A common thrombomodulin amino acid dimorphism is associated with myocardial infarction. Thromb Haemost, 1997, 77:248-251.
41. Ohlin AK, Holm J, Hillarp A. Genetic variation in the human thrombomodulin promoter locus and prognosis after acute coronary syndrome. Thromb Res, 2004, 113:319-326.
42. Zhao J, Zhou X, Huang J. Association study of the thrombomodulin -33G>A polymorphism with coronary artery disease and myocardial infarction in Chinese Han population. Int J Cardiol, 2005,28;100:383-388.
43. ROYLE NJ, NIGLI M, Cool D, et al. Structural gene encoding human factor XII islocated at 5q33-qter. Somat Cell Mol Genet. 1988, 14: 217-221.
44. COOL DE, MACGILLIVRAY RT. Characterization of the human blood coagulation factor XII gene. Intron/exon gene organization and analysis of the 5'-flanking region. J Biol Chem. 1987, 262: 13662-13673.
45. ZITO F, LOWE GD, RUMLEY A, et al. WOSCOPS Study Group West of Scotland Coronary Prevention Study. Association of the factor XII 46C>T polymorphism with risk of coronary heart disease (CHD) in the WOSCOPS study. Atherosclerosis. 2002, 165: 153-158.
46. ZITO F, DRUMMOND F, BUJAC SR, et al. Epidemiological and genetic associations of activated factor XII concentration with factor VII activity, fibrinopeptide A concentration, and risk of coronary heart disease in men. Circulation. 2000, 102: 2058-2062.
47. ENDLER G, MANNHALTER C, SUNDER-PLASSMANN H, et al. Homozygosity for the C->T polymorphism at nucleotide 46 in the 5' untranslated region of the factor XII gene protects from development of acute coronary syndrome. Br J Haematol. 2001, 115: 1007-1009.
48. KOHLER HP, FUTERS TS, GRANT PJ. FXII (46C-->T) polymorphism and in vivo generation of FXII activity--gene frequencies and relationship in patients with coronary artery disease. Thromb Haemost, 1999, 81: 745-747.
49. Steeds R, Adams M, Smith P, et al. Distribution of tissue plasminogen activator insertion/deletion polymorphism in myocardial infarction and control subjects. Thromb Haemost. 1998, 79:980-984.
50.宋杰.组织型纤溶酶原激活剂基因I/D多态性和内皮型一氧化氮合酶基因Glu-Asp298突变与心肌梗塞的相关性研究.博硕士学位论文全文数据库.2000.
51.张爱娟,张爱元,宋保华等.组织型纤溶酶原激活物抑制物基因多态性与脑梗死相关性的研究进展.国外医学神经病学神经外科学分册,2001,28:74-77.
52. Margaglione M, Cappucci G, Colaizzo D, et al. The PAI-1 gene locus 4G/5G polymorphism is associated with a family history of coronary artery disease. Arterioscler Thromb Vasc Biol, 1998,18:152-136.
53.季祥武,张爱元,管立学等.纤溶酶原激活剂抑制物-1基因启动子区4G/5G多态性与冠心病的相关性研究.中华心血管病杂志,2003,31:208-209.
54. Moatti D, Haidar B, Fumeron F, et al. A new T-287C polymorphism in the 5' regulatory region of the tissue factor pathway inhibitor gene. Association study of the T-287C and C-399T polymorphisms with coronary artery disease and plasma TFPI levels. Thromb Haemost, 2000,84:244-249.
55. Moatti D, Seknadji P, Galand C, et al. Polymorphisms of the tissue factor pathway inhibitor (TFPI) gene in patients with acute coronary syndromes and in healthy subjects : impact of the V264M substitution on plasma levels of TFPI. Arterioscler Thromb Vasc Biol, 1999,19:862-869.
2. Fareed J, Hoppensteadt DA, Leya F, et al. Useful laboratory tests for studying thrombogenesis in acute cardiac syndromes. Clin Chem,1998,44: 1845-1853.
3. Lisowski P, Malyszko J, Lisowska A, et al. Role of the hemostatic system in pathogenesis of atherosclerosis as the main etiology of coronary ischemia. Pol Merkur Lekarski,2004,16: 465-467.
4. Amiral J, Fareed J. Thromboembolic disease: biochemical mechanisms and new possibilities of biological diagnosis. Semin Thromb Hemost,1996,22:41-48.
5. Broze G, Miletich JP. Characterization of the inhibition of tissue factor in serum. Blood,1987,69:150-155.
6. Broze G, Warren J, Novotny LA, et al. The lipoprotein associated coagulation inhibitor that inhibits the factor VIIa-tissue factor complex, also inhibits factors Xa: insight into its possible mechanism of action. Blood,1988,71:335-343.
7. Bauer KA, Rosenberg RD. The pathophysiology of the prothrombotic state in humans: insight gained from studies using analytes of hemostatic system activation. Blood,1987,70: 343-350.
8. Messmore HL, Walenga JM, Fareed J. Molecular analytes of platelet activation. Semin Thromb Hemost,1984,10:264-269.
9. Aurousseau MH, Amiral J, Boffa MC. Level of plasma thrombomodulin in neonates and children. Thromb Hemost,1991,65:12-32.
10. Stephens CJM. The antiphospholipid syndrome. Clinical correlations, cutaneous features, mechanism of thrombosis and treatment of patients with the lupus anticoagulant and anticardiolinpin antibodies. Br J Dermatol, 1991,125:199-210.
11. Donner MG, Klein GK, Mathes PB, et al. Plasma total homocycteine levels in patients with early-onset coronary heart disease and a low cardiovascular risk profile. Metab Clin Exp,1998,47: 273-279.
12. Kohler HP, Carter AM, Stickland MH, et al. Level of activated FXII in survivors of myocardial infarction-association with circulating risk factors and extent of coronary artery disease. Thromb Hemost,1998,79: 14-18.
13. Steffel J, Luscher TF, Tanner FC. Tissue factor in cardiovascular diseases: molecular mechanisms and clinical implications. Circulation, 2006, 113: 722-731.
14. Tilley R, Mackman N. Tissue factor in hemostasis and thrombosis. Semin Thromb Hemost,2006,32: 5-10.
15. Mallat Z, Tedgui A. Current perspective on the role of apoptosis in atherothrombotic disease. Circ Res,2001,88: 998-1003.
16. Corti R, Fuster V,Badimon JJ. Pathogenetic concepts of acute coronary syndromes. J Am Coll Cardiol, 2003, 41:7-14.
17. Porreca E, Di Febbo C, di Castelnuovo A, et al. Association of factor VII levels with inflammatory parameters in hypercholesterolemic patients. Atherosclerosis, 2002,165: 159-166.
18. Heinrich J, Balleisen L, Schulte H, et al. Fibrinogen and factor VII in the prediction of coronary risk. Results from the PROCAM Study in healthy men. Arterioscler Thromb,1994,14:54-59.
19. 19 De Stavola BL and Meade TW. Long-term effects of hemostatic variables on fatal coronary heart disease: 30-year results from the first prospective Northwick Park Heart Study (NPHS-I). J Thromb Haemost, 2007,5:461-471.
20. Junker R, Heinrich J, Schulte H, et al. Coagulation factor VII and the risk of coronary heart disease in healthy men. Arterioscler Thromb Vasc Biol, 1997,17:1539-1544.
21. Folsom AR, Wu KK, Rosamond WD, et al. Prospective study of hemostatic factors and incidence of coronary heart disease. Circulation,1997,96: 1102-1108.
22. Tracy RP, Arnold AM, Ettinger W, et al. The relationship of fibrinogen and factor VII and VIII to incident cardiovascular disease and death in the elderly. Results from the cardiovascular health study. Arterioscler Thromb Vasc Biol,1999,19: 1776-1783.
23. Cooper JA, Miller GJ, Bauer KA, et al. Comparison of novel hemostatic factors and conventional risk factors for prediction of coronary heart disease. Circulation, 2000, 102:2816-2822.
24. Woodhouse PR, Khaw KT, Plummer M, et al. Seasonal variations of plasma fibrinogen and factor VII activity in the elderly: winter infections and death from cardiovascular disease. Lancet,1994,343: 435-439.
25. Ridker PM. Fibrinolytic and inflammatory markers for arterial occlusion: the evolving epidemiology of thrombosis and haemostasis. Thromb Haemost, 1997, 78: 53-59.
26. Laffan MA. Activated protein C resistance and myocardial infarction. Heart, 1998,80: 319-321.
27. Kabukcu S, Keskin N, Kesdin A, et al. The frequency of factor V Leiden and concomitance of factor V Leiden with prothrombin G20210A mutation and methylene tetrahydrofolate reductase C677T gene mutation in healthy population of Denizli, Aegean region of Turkey. Clin Appl Thromb Hemost, 2007, 13: 166-171.
28.马爱华,李牧尧,康福信,等.新疆地区汉族和哈萨克族正常人群中FV Leiden突变的初步调查.中华血液学杂志,1999,20: 267.
29. Wu J, Gu J, Xu J, et a1.Factor V Leiden mutation in one family of Chinese origin. Chin Med J, 2001, 114: 379-381.
30.罗佳滨,关月,马洪星,等.凝血因子V基因突变1691A在不同种族人群中的分布.中华医学遗传学杂志,1996,13: 219-220.
31. Rosendorff A, Dorfman DM. Activated protein C resistance and factor V Leiden: a review. Arch Pathol Lab Med, 2007, 131: 866-871.
32. Sakata T, Kario K, Katayama Y, et al. Clinical significance of activated protein C resistance as a potential marker for hypercoagulable state. Thromb Res, 1996, 82: 235-244.
33. Avellone G, Di Garbo V, Di Raimondo D, et al. Evaluation of resistance to activated protein C in myocardial infarction patients. Minerva Cardioangiol,2001,49: 363-368.
34. Makris TK, Krespi PG, Hatzizacharias AN, et al. Resistance to activated protein C and FV leiden mutation in patients with a history of acute myocardial infarction or primary hypertension. Am J Hypertens, 2000,13: 61-65.
35. Hayashi K, Sone T, Kondoh J, et al. Prevalence of activated protein C resistance in acute myocardial infarction in Japan. Jpn Heart J, 1997, 38: 769–778.
36. Prohaska W, Mannebach H, Schmidt M, et al. Evidence against heterozygous coagulation factor V 1691 G-->A mutation with resistance to activated protein C being a risk factor for coronary artery disease and myocardial infarction. J Mol Med,1995,73:521-524.
37.郑延松,郑秋甫.活化蛋白C抵抗现象与血栓性疾病的关系.国外医学心血管疾病分册,2004,31: 87-89.
38. Salomaa V, Matei C, Aleksic N, et al. Soluble thrombomodulin as a predictor of incident coronary heart disease and symptomless carotid artery atherosclerosis in the Atherosclerosis Risk in Communities (ARIC) Study: a case-cohort study. Lancet, 1999,353:1729-1734.
39. Blann AD, Amiral J, McCollum CN. Prognostic value of increased soluble thrombomodulin and increased soluble E-selectin in ischaemic heart disease. Eur J Haematol,1997, 59:115-120.
40. Wu KK. Soluble thrombomodulin and coronary heart disease . Curr Opin Lipidol, 2003, 14: 373-375.
41. Olivot JM, Labreuche J, Aiach M, et al. Soluble thrombomodulin and brain infarction: case-control and prospective study. Stroke,2004,35: 1946-1951.
1.杨旭玲,裴晓冬.心肌肌钙蛋白T在急性冠脉综合症诊断中的意义.中国实验诊断学,2007,11:23-24.
2. Alpert JS, Thygesen K, Antman E, et al. Myocardial infarction redefined-A consensus document of the European Society of Cardiology/American college of Cardiology Committee for the redefinition of myocardial infarction. J Am Coll Cardial,2000,36: 959-969.
3.陈绍良.急性心肌梗死细胞再生治疗进展.临床内科杂志,2007,24:5-7.
4. Rodland KD. Proteomics and cancer diagnosis: the potential of mass spectrometry. Clinical Biochemistry, 2004, 37: 579-583.
5. Poon TC, Yip TT, Chan AT, et al. Comprehensive proteomic profiling identifies serum proteomic signatures for detection of hepatocellular carcinoma and its subtypes. Clin Chem, 2003, 49: 752–760.
6. Grus FH, Podust VN, Bruns K, et al.SELDI-TOF-MS proteinchip array profiling of tears from patients with dry eye. Invest Ophthalmol Vis Sci, 2005, 46: 863-876.
7.褚福亮,王福生.蛋白质谱分析方法特点及其在蛋白组学研究领域中的应用.世界华人消化杂志,2002,10:1431-1435.
8. Liu Y. Active learning with support vector machine applied to gene expression data for cancer classification. J Chem Inf Comput Sci, 2004, 44: 1936-1941.
9. Hutchens TW, Yip TT. New desorption strategies for the mass spectrometric analysis of macromolecules. Rapid Comm Mass Spectrum, 1993,7:576-580.
10. Smith RD, Anderson GA,Lipton MS, et al. An accurate mass tag strategy for quantitative and high-throughput proteme measurements. Proteomics, 2002, 2:513-523.
11. Foret F, Preisler J. Liquid phase interfacing and miniaturization in matrix-assisted laser desorption/ionixation mass spectrometry. Proteomics, 2002, 2: 360-370.
12.罗治文.质谱技术研究进展.国外医学生物医学工程分册.2005,28:134-137.
13. Wright GL, Cazares LH, Leung SM. ProteinChip surface enhanced laser desorption/ionization (SELDI) mass spectromatry: a novel protein biochip technologyfor detection of biomarker in complex protein mixtures. Prostate Cancer Prostatic Dis, 2000,2:264-276.
14. Amiral J, Fareed J. Thromboembolic diseases: biochemical mechanisms and new possibilities of biological diagnosis. Semin Thromb Hemost, 1996, 22: 41-48.
15.胡跃,张苏展,余捷凯等.乳腺癌患者血清蛋白质指纹图谱检测及其临床意义.中华检验医学杂志,2004,27: 646-648.
16. Baggerly KA, Morris JS, Coombes KR. Reproducibility of SELDI-TOF protein patterns in serum:comparing datasets from different experiments. Bioinformatics, 2004,20: 777–785.
17. Seibert V, Ebert MP, Buschmann T. Advances in clinical cancer proteomics: SELDI-TOF-mass spectrometry and biomarker discovery. Brief Funct Genomic Proteomic,2005,4:16-26.
18. Liotta LA, Lowenthal M, Mehta A, et al. Importance of communication between producers and consumers of publicly available experimental data. J Natl Cancer Inst,2005,97: 310-314.
19. Banks RE, Stanley AJ, Cairns DA, et al. Influences of blood sample processing on low-molecular-weight proteome identified by surface-enhanced laser desorption/ ionization mass spectrometry. Clin Chem, 2005, 51: 1637-1649.
20. Byvatov E, Schneider G. Support vector machine applications in bioinformatics. Appl Bioinformatics, 2003, 2: 67-77.
21. Jorissen RN, Gilson MK. Virtual screening of molecular databases using a support vector machine. J Chem Inf Model, 2005, 45: 549-561.
1.王晓玲,顾东风.冠心病遗传因素的研究进展.中华医学遗传学杂志,2000,17:452-454.
2.谭光波,毛以林,袁肇凯.冠心病基因多态性研究进展.中西医结合心脑血管病杂志,2004,2:98-100.
3. Yoneya K, Okamoto H, Kitabatake A. Genetic polymorphisms as risk factors for coronary artery disease. Nippon Rinsho, 1998,56:2509-2514.
4. Taylor G R and Deeble J. Enzymatic methods for mutation scanning. Genet Anal,1999,14:181–186.
5. Fodde R and Losekoot M. Mutation detection by denaturing gradient gel electrophoresis (DGGE). Hum Mutat,1994,3:83–94.
6. Lancaster JM, Berchuck A, Futreal P A, et al. Dideoxy fingerprinting assay for BRCA1 mutation analysis. Mol Carcinog.1997,19: 176–179.
7. Markoff A, Savov A, Vladimirov V, et al. Optimization of single-strand conformation polymorphism analysis in the presence of polyethylene glycol. Clin Chem, 1997,43:30–33.
8. Hedberg JJ, Backlund M, Stromberg P, et al. Functional polymorphism in the alcohol dehydrogenase 3 (ADH3) promoter. Pharmacogenetics, 2001,11: 815–824.
9. Markoff A, Sormbroen H, Bogdanova N, et al. Comparison of conformation-sensitive gel electrophoresis and single-strand conformation polymorphism analysis for detection of mutations in the BRCA1 gene using optimized conformation analysis protocols. Eur J Hum Genet, 1998, 6: 145–150.
10. Ezzeldin H, Okamoto Y, Johnson MR, et al. A High-Throughput Denaturing High-Performance Liquid Chromatography Method for the Identification of Variant Alleles Associated with Dihydropyrimidine Dehydrogenase Deficiency. Anal Biochem, 2002, 306:63-73.
11. Taylor JD, Briley D, Nguyen Q, et al. Flow cytometric platform for high-throughput single nucleotide polymorphism analysis. Biotechniques,2001,30:661-666, 668-669.
12.张华宁,高雪芹,韩金祥.多色微球液相芯片技术的原理及其应用.山东医药,2006,46:71-72.
13.何英,陆学东.液相芯片技术及其临床应用.国际检验医学杂志,2006,27:1107-1111.
14.牟颖,金钦汉.荧光编码微球-流式细胞和生化分析技术及其最新发展.2003,1:31-36.
15.王蕾,吴英松,李明.液相芯片分析技术及其应用简介.热带医学杂志,2005,5:562-564.
16. Biagini RE, Sammons DL, Smith JP. Comparison of a multiplexed fluorescent covalent microsphere immunoassay and an enzyme-linked immunosorbent assay for measurement of human immunoglobulin G antibodies to anthrax toxins. Clin Diagn Lab Immunol, 2004,11:50-55.
17. Nata M, Hashiyada M. Analysis of the single nucleotide polymorphism of mitochondrial DNA by liquid bead array technology. Int Congr Ser, 2004, 1261:369-371.
18. Deregt D, Gilbert SA, Dudas S, et al.A multiplex DNA suspension microarray for simultaneous detection and differentiation of classical swine fever virus and other pestiviruses. J Virol Methods, 2006,136:17-23.
19. Hadd AG, Laosinchai-Wolf W, Novak CR. Microsphere bead arrays and sequence validation of 5/7/9T genotypes for multiplex screening of cystic fibrosis polymorphisms. J of Mol Diagnos, 2004,6:348-355.
20. Bellisario R ,Colinas RJ , Pass KA. Simultaneous measurement of thyroxine and thyrotropin from newborn dried blood-spot specimens using a multiplexed fluorescent microsphere immunoassay. Clin Chem ,2000 ,46 :1422-1424.
21. Dahlback B, Carlsson M, Svensson PJ.Familial thrombophilia due to a previously unrecognized mechanism characterized by poor anticoagulant response to activated protein C: prediction of a cofactor to activated protein C. Proc Natl Acad Sci USA, 1993, 90:1004-1008.
22. Bertina RM, Koeleman BP, Koster T, et a1.Mutation in blood coagulation factor Vassociated with resistance to activated protein C.Nature, 1994, 369: 64-67.
23. Khare A, Ghosh K, Shetty S, et al. Combination of thrombophilia markers in acute myocardial infarction of the young. Indian J Med Sci, 2004, 58:381-388.
24. Tanis BC, Bloemenkamp DG, van den Bosch MA, et al. Prothrombotic coagulation defects and cardiovascular risk factors in young women with acute myocardial infarction. Br J Haematol, 2003, 122:471-478.
25.马爱华,李牧尧,康福信,等.新疆地区汉族和哈萨克族正常人群中FV Leiden突变的初步调查.中华血液学杂志,1999,20: 267.
26. Wu J, Gu J, Xu J, et a1.Factor V Leiden mutation in one family of Chinese origin.Chin Med J, 2001, 114: 379-381.
27.罗佳滨,关月,马洪星,等.凝血因子V基因突变1691A在不同种族人群中的分布.中华医学遗传学杂志,1996,13: 219-220.
28. Burzotta F, Paciaroni K, De Stefano V, et al. G20210A prothrombin gene polymorphism and coronary ischaemic syndromes: a phenotype-specific meta-analysis of 12 034 subjects. Heart, 2004,90:82-86.
29. Lane DA, Grant PJ. Role of hemostatic gene polymorphism in venous and arterial thrombotic disease. Blood, 2000, 95:1517-1532.
30.陶蓉,于金德,陆林等.凝血因子VII活性与多态性关系的研究.中华心血管病杂志,2000,28:27-29.
31. Campo G, Valgimigli M, Ferraresi P,et al. Tissue factor and coagulation factor VII levels during acute myocardial infarction: association with genotype and adverse events. Arterioscler Thromb Vasc Biol, 2006, 26:2800-2806.
32. Rothenbacher D,Fischer HG,Hoffmeister A,et al. Homocysteine and methylenetetrahydrofolate reductase genotype:association with resk of coronary heart disease and relation to inflammatory,hemostatic,and lipid parameters. Atherosclerosis, 2002,162:193-200.
33.祝鸿喜,马向红,黄体钢等.MTHFR基因多态性与冠心病的关系.实用心脑肺血管病杂志,2007,15:569-572.
1. REVAK SD, COCHRANE CG, JOHNSTON AR, et al. Structural changes accompanying enzymatic activation of human Hageman factor. J Clin Invest. 1974, 54: 619-627.
2. KANAJI T, OKAMURA T, OSAKI K, et al. A common genetic polymorphism (46 C to T substitution) in the 5'-untranslated region of the coagulation factor XII gene is associated with low translation efficiency and decrease in plasma factor XII level. Blood. 1998, 91: 2010-2014.
3. COOL DE, EDGELL CJ, LOUIE GV, et al. Characterization of human blood coagulation factor XII cDNA. Prediction of the primary structure of factor XII and the tertiary structure of beta-factor XIIa. J Biol Chem. 1985, 260:13666-13676.
4.周运恒,王鸿利.凝血因子XII与纤维蛋白溶解的关系.医学综述, 2002, 8(4): 223-224.
5. ROYLE NJ, NIGLI M, Cool D, et al. Structural gene encoding human factor XII is located at 5q33-qter. Somat Cell Mol Genet. 1988, 14: 217-221.
6. COOL DE, MACGILLIVRAY RT. Characterization of the human blood coagulation factor XII gene. Intron/exon gene organization and analysis of the 5'-flanking region. J Biol Chem. 1987, 262: 13662-13673.
7. ENDLER G, EXNER M, MANNHALTER C, et al. A common C-->T polymorphism at nt 46 in the promoter region of coagulation factor XII is associated with decreased factor XII activity. Thromb Res. 2001, 101: 255-260.
8. KONDO S, TOKUNAGA F, KAWANO S, et al. Factor XII Tenri, a novel cross-reacting material negative factor XII deficiency, occurs through a proteasome-mediated degradation. Blood. 1999, 93: 4300-4308.
9. HOFFERBERT S, MULLER J, KOSTERING H, et al. A novel 5'-upstream mutation in the factor XII gene is associated with a TaqI restriction site in an Alu repeat in factor XII-deficient patients. Hum Genet. 1996, 97: 838-841.
10. SCHLOESSER M, HOFFERBERT S, BARTZ U, et al. The novel acceptor splice site mutation 11396(G-->A) in the factor XII gene causes a truncated transcript incross-reacting material negative patients. Hum Mol Genet. 1995, 4: 1235-1237.
11. KANAJI T, KANAJI S, OSAKI K, et al. Identification and characterization of two novel mutations (Q421 K and R123P) in congenital factor XII deficiency. Thromb Haemost. 2001, 86: 1409-1415.
12. KANAJI T, OKAMURA T, OSAKI K, et al. A common genetic polymorphism (46 C to T substitution) in the 5'-untranslated region of the coagulation factor XII gene is associated with low translation efficiency and decrease in plasma factor XII level. Blood. 1998, 91: 2010-2014.
13. ISHII K, OGUCHI S, MURATA M, et al. Activated factor XII levels are dependent on factor XII 46C/T genotypes and factor XII zymogen levels, and are associated with vascular risk factors in patients and healthy subjects. Blood Coagul Fibrinolysis. 2000, 11: 277-284.
14. SANTAMARIA A, MATEO J, TIRADO I, et al. Homozygosity of the T allele of the 46 C->T polymorphism in the F12 gene is a risk factor for ischemic stroke in the Spanish population. Stroke. 2004, 35: 1795-1799.
15. OGUCHI S, ITO D, MURATA M, et al. Genotype distribution of the 46C/T polymorphism of coagulation factor XII in the Japanese population: absence of its association with ischemic cerebrovascular disease. Thromb Haemost. 2000, 83: 178-179.
16. ZITO F, LOWE GD, RUMLEY A, et al. WOSCOPS Study Group West of Scotland Coronary Prevention Study. Association of the factor XII 46C>T polymorphism with risk of coronary heart disease (CHD) in the WOSCOPS study. Atherosclerosis. 2002, 165: 153-158.
17. ZITO F, DRUMMOND F, BUJAC SR, et al. Epidemiological and genetic associations of activated factor XII concentration with factor VII activity, fibrinopeptide A concentration, and risk of coronary heart disease in men. Circulation. 2000, 102: 2058-2062.
18. ENDLER G, MANNHALTER C, SUNDER-PLASSMANN H, et al. Homozygosity for the C-->T polymorphism at nucleotide 46 in the 5' untranslated region of the factor XII gene protects from development of acute coronary syndrome. Br J Haematol.2001, 115: 1007-1009.
19. KOHLER HP, FUTERS TS, GRANT PJ. FXII (46C-->T) polymorphism and in vivo generation of FXII activity--gene frequencies and relationship in patients with coronary artery disease. Thromb Haemost. 1999, 81: 745-747.
20. TIRADO I, SORIA JM, MATEO J, et al. Association after linkage analysis indicates that homozygosity for the 46C-->T polymorphism in the F12 gene is a genetic risk factor for venous thrombosis. Thromb Haemost. 2004, 91: 899-904.
21. ORTH M, WESTPHAL S, DIERKES J, et al. Rapid factor XII (46C-->T) genotyping by fluorescence resonance energy transfer in patients with coronary artery disease or thrombophilia. Clin Chem. 2001, 47: 1117-1119.
1. Bertina RM, Koeleman BP, Koster T, et a1.Mutation in blood coagulation factor V associated with resistance to activated protein C.Nature, 1994, 369: 64-67.
2. Nicolaes GA, Tans G, Thomassen MC, et at. Peptide bond cleavages and loss of functiona1 activity during inactivation of factor Va and factor VaR506Q by activated protein C.J Bio1 Chem, 1995, 270: 21158-21166.
3. Chan WP, Lee CK, Kwong YL, et al. A Novel mutation of Arg306 of factor V gene in Hong Kong Chinese. Blood, 1998, 91:1135-1139.
4. Williamson D, Brown K, Luddington R, et a1.Factor V Cambridge: a new mutation(Arg306→Thr) associated with resistance to activated protein C.Blood, 1998, 91: l140-l144.
5. Kabukcu S, Keskin N, Kesdin A, et al. The frequency of factor V Leiden and concomitance of factor V Leiden with prothrombin G20210A mutation and methylene tetrahydrofolate reductase C677T gene mutation in healthy population of Denizli, Aegean region of Turkey. Clin Appl Thromb Hemost, 2007, 13: 166-171.
6.马爱华,李牧尧,康福信,等.新疆地区汉族和哈萨克族正常人群中FV Leiden突变的初步调查.中华血液学杂志,1999,20: 267.
7. Wu J, Gu J, Xu J, et a1.Factor V Leiden mutation in one family of Chinese origin.Chin Med J, 2001, 114: 379-381.
8.罗佳滨,关月,马洪星,等.凝血因子V基因突变1691A在不同种族人群中的分布.中华医学遗传学杂志,1996,13: 219-220.
9. Khare A, Ghosh K, Shetty S, et al. Combination of thrombophilia markers in acute myocardial infarction of the young. Indian J Med Sci, 2004, 58:381-388.
10. Tanis BC, Bloemenkamp DG, van den Bosch MA, et al. Prothrombotic coagulation defects and cardiovascular risk factors in young women with acute myocardial infarction. Br J Haematol, 2003, 122:471-478.
11. Doix S, Mahrousseh M, Jolak M, et al. Factor V Leiden and myocardial infarction: acase, review of the literature with a meta-analysis. Ann Cardiol Angeiol (Paris), 2003,52:143-149.
12. D?nmez Y, Kanadasi M, Tanriverdi K, et al. Prothrombin 20210GA and factor V Leiden mutations in patients less than 55 years old with myocardial infarction. Jpn Heart J, 2004, 45:505-512.
13. Yanqing H, Fangping C, Qinzhi X, et al. No association between thrombosis and factor V gene polymorphisms in Chinese Han population. Thromb Haemost, 2003, 89:446-451.
14. Baykan M, Celik S, U?ar F, et al. Effects of factor V Leiden mutations on prognosis in patients with acute myocardial infarction. Anadolu Kardiyol Derg, 2001,1:242-245; AXIV.
15. Gowda MS, Zucker ML, Vacek JL, et al. Incidence of factor V Leiden in patients with acute myocardial infarction. J Thromb Thrombolysis, 2000, 9:43-45.
16. Lane DA, Grant PJ. Role of hemostatic gene polymorphism in venous and arterial thrombotic disease. Blood, 2000, 95:1517-1532.
17. de Maat MP, Kastelein JJ, Jukema JW, et al. -455G/A polymorphism of the beta-fibrinogen gene is associated with the progression of coronary atherosclerosis in symptomatic men: proposed role for an acute-phase reaction pattern of fibrinogen. REGRESS group. Arterioscler Thromb Vasc Biol, 1998,18:265-271.
18.马会利,陈纪林,冯军等.年轻心肌梗死患者纤维蛋白原基因βG455A多态性研究.中华心血管病杂志,2002,30:74-77.
19. Zito F, Di Castelnuovo A, Amore C, et al. Bcl I polymorphism in the fibrinogen beta-chain gene is associated with the risk of familial myocardial infarction by increasing plasma fibrinogen levels. A case-control study in a sample of GISSI-2 patients. Arterioscler Thromb Vasc Biol, 1997, 17:3489-3494.
20.王晓明,张桂茹,马学玲等.缺血性心脏病与β-纤维蛋白原基因bcl-I多态性和血浆纤维蛋白原水平的关系.吉林大学学报(医学版), 2005,31:791-794.
21. Girelli D, Russo C, Ferraresi P, et al. Polymorphisms in the factor VII gene and the risk of myocardial infarction in patients with coronary artery disease. N Eng J Med, 2000,343:774-780.
22. Heywood DM, Ossei-Gerning N, Grant PJ. Association of factor VII:C levels with environmental and genetic factors in patients with ischaemic heart disease and coronary atheroma characterised by angiography. Thromb Haemost, 1996, 76:161-165.
23. Campo G, Valgimigli M, Ferraresi P,et al. Tissue factor and coagulation factor VII levels during acute myocardial infarction: association with genotype and adverse events. Arterioscler Thromb Vasc Biol, 2006, 26:2800-2806.
24. Carew JA, Basso F, Miller GJ, et al. A functional haplotype in the 5' flanking region of the factor VII gene is associated with an increased risk of coronary heart disease. J Thromb Haemost, 2003, 1:2179-2185.
25. Batalla A, Alvarez R, Reguero JR, et al. Lack of association between polymorphisms of the coagulation factor VII and myocardial infarction in middle-aged Spanish men. Int J Cardiol, 2001, 80:209-212.
26. Feng YJ, Draghi A, Linfert DR, et al. Polymorphisms in the genes for coagulation factors II, V, and VII in patients with ischemic heart disease. Arch Pathol Lab Med, 1999, 123:1230-5120.
27. Ariens RA, Philipou H, Nagaswami C, et al. The factor XIII Val34Leu polymorphism accelerates theombin activation of factor XIII and affects cross-linked fibrin structure. Blood, 2000, 96:988-995.
28. Kakko S, Elo T, Tapanainen JM, et al. Polymorphisms of genes affecting thrombosis and risk of myocardial infarction. Eur J Clin Invest, 2002, 32:643-648.
29. Kohler HP, Stickland MH, Ossei-Gerning N, et al. Association of a common polymorphism in the factor XIII gene with myocardial infarction. Thromb Haemost, 1998,79:8-13.
30. Shafey M, Anderson JL, Scarvelis D, et al. Factor XIII Val34Leu variant and the risk of myocardial infarction: a meta-analysis. Thromb Haemost, 2007,97:635-641.
31. Burzotta F, Paciaroni K, De Stefano V, et al. G20210A prothrombin gene polymorphism and coronary ischaemic syndromes: a phenotype-specific meta- analysis of 12 034 subjects. Heart, 2004,90:82-86.
32. Burzotta F, Paciaroni K, De Stefano V, et al. Increased prevalence of the G20210Aprothrombin gene variant in acute coronary syndromes without metabolic or acquired risk factors or with limited extent of disease. Eur Heart J, 2002, 23:26-30.
33. Croft SA, Daly ME, Steeds RP, et al. The prothrombin 20210A allele and its association with myocardial infarction. Thromb Haemost, 1999, 81:861-864.
34. Eikelboom JW, Baker RI, Parsons R, et al. No association between the 20210 G/A prothrombin gene mutation and premature coronary artery disease. Thromb Haemost, 1998,80:878-880.
35.唐雪元,陈方平,解勤之等.急性心肌梗死患者凝血酶原基因G20210A变异频度分析.中国现代医学杂志.2002,12:33-37.
36.钱高潮,李稻,王鸿利.血栓调节蛋白基因变异的研究进展.国外医学输血及血液学分册,2002,25:193-195.
37. Chao TH, Li YH, Chen JH, et al. Relation of thrombomodulin gene polymorphisms to acute myocardial infarction in patients
39. Li YH, Chen JH, Tsai WC, et al. Synergistic effect of thrombomodulin promoter -33G/A polymorphism and smoking on the onset of acute myocardial infarction. Thromb Haemost, 2002,87:86-91.
40. Norlund L, Holm J, Z?ller B, et al. A common thrombomodulin amino acid dimorphism is associated with myocardial infarction. Thromb Haemost, 1997, 77:248-251.
41. Ohlin AK, Holm J, Hillarp A. Genetic variation in the human thrombomodulin promoter locus and prognosis after acute coronary syndrome. Thromb Res, 2004, 113:319-326.
42. Zhao J, Zhou X, Huang J. Association study of the thrombomodulin -33G>A polymorphism with coronary artery disease and myocardial infarction in Chinese Han population. Int J Cardiol, 2005,28;100:383-388.
43. ROYLE NJ, NIGLI M, Cool D, et al. Structural gene encoding human factor XII islocated at 5q33-qter. Somat Cell Mol Genet. 1988, 14: 217-221.
44. COOL DE, MACGILLIVRAY RT. Characterization of the human blood coagulation factor XII gene. Intron/exon gene organization and analysis of the 5'-flanking region. J Biol Chem. 1987, 262: 13662-13673.
45. ZITO F, LOWE GD, RUMLEY A, et al. WOSCOPS Study Group West of Scotland Coronary Prevention Study. Association of the factor XII 46C>T polymorphism with risk of coronary heart disease (CHD) in the WOSCOPS study. Atherosclerosis. 2002, 165: 153-158.
46. ZITO F, DRUMMOND F, BUJAC SR, et al. Epidemiological and genetic associations of activated factor XII concentration with factor VII activity, fibrinopeptide A concentration, and risk of coronary heart disease in men. Circulation. 2000, 102: 2058-2062.
47. ENDLER G, MANNHALTER C, SUNDER-PLASSMANN H, et al. Homozygosity for the C->T polymorphism at nucleotide 46 in the 5' untranslated region of the factor XII gene protects from development of acute coronary syndrome. Br J Haematol. 2001, 115: 1007-1009.
48. KOHLER HP, FUTERS TS, GRANT PJ. FXII (46C-->T) polymorphism and in vivo generation of FXII activity--gene frequencies and relationship in patients with coronary artery disease. Thromb Haemost, 1999, 81: 745-747.
49. Steeds R, Adams M, Smith P, et al. Distribution of tissue plasminogen activator insertion/deletion polymorphism in myocardial infarction and control subjects. Thromb Haemost. 1998, 79:980-984.
50.宋杰.组织型纤溶酶原激活剂基因I/D多态性和内皮型一氧化氮合酶基因Glu-Asp298突变与心肌梗塞的相关性研究.博硕士学位论文全文数据库.2000.
51.张爱娟,张爱元,宋保华等.组织型纤溶酶原激活物抑制物基因多态性与脑梗死相关性的研究进展.国外医学神经病学神经外科学分册,2001,28:74-77.
52. Margaglione M, Cappucci G, Colaizzo D, et al. The PAI-1 gene locus 4G/5G polymorphism is associated with a family history of coronary artery disease. Arterioscler Thromb Vasc Biol, 1998,18:152-136.
53.季祥武,张爱元,管立学等.纤溶酶原激活剂抑制物-1基因启动子区4G/5G多态性与冠心病的相关性研究.中华心血管病杂志,2003,31:208-209.
54. Moatti D, Haidar B, Fumeron F, et al. A new T-287C polymorphism in the 5' regulatory region of the tissue factor pathway inhibitor gene. Association study of the T-287C and C-399T polymorphisms with coronary artery disease and plasma TFPI levels. Thromb Haemost, 2000,84:244-249.
55. Moatti D, Seknadji P, Galand C, et al. Polymorphisms of the tissue factor pathway inhibitor (TFPI) gene in patients with acute coronary syndromes and in healthy subjects : impact of the V264M substitution on plasma levels of TFPI. Arterioscler Thromb Vasc Biol, 1999,19:862-869.