脂蛋白脂酶基因多态性和动脉粥样硬化性脑梗死相关性的研究
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摘要
目的:国内外大量研究表明,脂蛋白脂酶(LPL)不同位点的基因多态性对血脂水平(尤为甘油三酯,TG)有一定影响,而高甘油三酯血症(Hypertriglyceridaemia,HTG)又是动脉粥样硬化性脑梗死(atherosclerotic cerebral infarction,ACI)的重要危险因素。本研究主要探讨中国河北汉族人群LPL基因PvuⅡ及N291S单核苷酸多态性与高甘油三酯血症及动脉粥样硬化性脑梗死的关系。
方法:对41例动脉粥样硬化性脑梗死患者和88例人群随机挑选对照进行病例对照研究。运用多聚酶链反应-限制性内切酶片段长度多态性(PCR-RFLP)分析技术分别检测LPL基因PvuⅡ及N291S多态性,并测定血清TG含量。分析高血压、糖尿病、高血脂、吸烟、体重指数及LPL基因PvuⅡ及N291S多态性位点与ACI发病的相关性。
结果
1 ACI组与对照组的一般情况:两组人群的年龄和性别比例没有统计学差异。ACI组的BMI高于对照组,但无统计学意义(P>0.05),有吸烟史、糖尿病史和高血压病史者明显多于对照组(P<0.05)。
2两组中PvuⅡ位点基因型均以P+P-型多见,其次为P+P+型,而P-P-型比较少见;其等位基因频率分布均以P+等位基因为常见等位基因,P-等位基因为少见等位基因。两组人群中PvuⅡ多态性基因型分布符合Hardy-Weinberg平衡,具有群体代表性。ACI组和对照组P+P+、P+P-、P-P-基因型频率分别为0.341vs0.295、0.512vs0.534、0.147vs0.171,差异无统计学意义(P>0.05);两组P+、P-等位基因频率分别为0.598 vs0.563、0.402vs0.437,差异亦无统计学意义(P>0.05)。
3 ACI组中P+P+、P+P-、P-P-基因型的血清TG水平逐渐递减(3.50±2.32vs2.75±2.07vs1.88±1.04),但无统计学差异(F=1.44,P=0.2504);对照组中P+P+、P+P-、P-P-基因型的血清TG水平分别为(2.07±0.61vs1.88±0.57vs1.87±0.57),三者比较差异亦无统计学意义(F=1.01,P=0.3672)。
4 ACI组中HTG、NTG亚组P+P+型、P+P-型、P-P-型频率分别为37.0%vs28.6%、55.6%vs42.9%、7.4%vs28.5%,两亚组比较无统计学差异(X2=0.038,P =0.846>0.05),P+、P-等位基因频率分别为64.8%vs50.0%、35.2%vs50.0%,差异亦无统计学意义(P>0.05);对照组中HTG、NTG亚组P+P+型、P+P-型、P-P-型频率分别为22.4%vs38.5%、57.1%vs48.7%、11.5%vs12.8%,两亚组比较无统计学差异(X2=2.907,P = 0.234>0.05),P+、P-等位基因频率分别为51.0%vs62.8%、49.0%vs37.2%,差异亦无统计学意义(P>0.05)。
5以是否患ACI为应变量,高血压、糖尿病、吸烟、携带P+等位基因、肥胖(BMI)等ACI常见危险因素为自变量,进行多因素Logistic回归分析,以a =0.1为入选和排除标准,结果发现吸烟史(OR=3.367)、高血压病史(OR=3.185)、糖尿病病史(OR=3.409)进入模型,是ACI的独立危险因素;而携带P+等位基因则未进入模型,不是ACI的独立危险因素。
6 N291S突变在病对两组中均未发现。
结论
1 LPL基因P+等位基因与血清TG水平无明显相关性。
2 LPL基因P+等位基因与ACI发生不相关,可能不足以构成ACI的独立遗传性危险因子。
3 LPL基因N291S突变在病对两组中均未发现,推测在欧洲白种人存在的与HTG、ACI的发生相关联的LPL常见基因变异N291S可能与中国人HTG、ACI的发生无关。
4吸烟史、高血压史、糖尿病史是ACI的独立危险因素,与以往认识相符。
5本组实验未发现肥胖与ACI发生存在直接相关性。
Objective: Many Researches show that, different gene polymorphisms of Lipoprotein lipase(LPL) have certain effects on blood lipids (especially on triglyceride , TG), while hypertriglyceridemia(HTG) is an important risk factor for atherosclerotic cerebral infarction(ACI). The aim of this study is to investigate the association of PvuⅡand N291S polymorphisms in LPL gene with HTG and ACI.
Methods: The genotype and allele frequencies of LPL gene polymorphisms (PvuⅡand N291S) were analyzed by PCR-restriction fragment length polymorphism in 41 ACI patients and 88 random-selected healthy control individuals. Meanwhile serum triglyceride levels were determined. The correlation of high blood pressure, diabetes, high cholesterol, smoking, body mass index, PvuⅡand N291S gene polymorphisms with the incidence of ACI were also analyzed.
Results
1 The general state of ACI group and the control group: In two groups there was no difference between the age and sex ratio. ACI group of patients have higher body mass index without statistical significance (P>0.05), but Significantly higher smoking rates, prevalence of hypertension and diabetes compared with the control group (P<0.05).
2 In the two groups, P+P- genotype were prevalent, followed by P+P+ and P-P- is relatively rare; P+ is the main allele and P- is the rare allele. The genotype distribution of PvuⅡin both groups corresponds to Hardy-Weinberg equilibrium, with groups’representation. In ACI group and the control group, P+P+、P+P-、P-P- genotype frequencies are 0.341vs0.295, 0.512vs0.534, 0.147vs0.171 respectively, without statistical significance (P>0.05); P+、P- allele frequencies are 0.598vs0.563, 0.402vs0.437 respectively, the differences between the two groups were also without statistically significant (P>0.05).
3 In ACI group, serum triglyceride concentrations of P+P+、P+P-、P-P- genotype are 3.50±2.32vs2.75±2.07vs1.88±1.04 respectively, exhibiting a gradual decrease, but without statistical significance(F=1.44,P=0.2504). In control group, serum triglyceride concentrations of P+P+、P+P-、P-P- genotype are 2.07±0.61vs1.88±0.57vs1.87±0.57 respectively, also without statistically significant differences among the three(F=1.01,P= 0.3672).
4 In HTG and NTG subgroups of ACI group, P+P+、P+P-、P-P- genotype frequencies are 0.370vs0.286, 0.556vs0.429, 0.074vs0.285 respectively, without statistical significance (X2= 0.038,P= 0.846>0.05). P+、P- allele frequencies are 0.648vs 0.500, 0.352vs0.500 respectively, without statistical significance (P>0.05). In HTG and NTG subgroups of the controls, P+P+、P+P-、P-P- genotype frequencies are 0.224vs0.385, 0.571vs 0.487, 0.115vs0.128 respectively, without statistical significance (X2=2.907,P=0.234>0.05). P+、P- allele frequencies are 0.510 vs0.628, 0.490vs0.372, without statistical significance(P>0.05).
5 A multivariate logistic regression analysis, with a =0.1 as the selective and exclusive criterion. The dependent variable was getting the ACI or not and the independent variables included hypertension, diabetes, smoking, carrying P+ allele, obesity(BMI) and other risk factors for ACI. It is found that smoking history, hypertension, diabetes were brought into the model, as independent risk factors for ACI; while carrying P+ allele was not.
6 N291S mutation of LPL was not found in either group.
Conclusion
1 The allele P+ had no significant correlation with serum triglyceride levels.
2 The allele P+, which had no association with ACI, couldn’t be regarded as one of the independent genetic risk factors for ACI in Chinese population.
3 N291S mutation of LPL, which had certain association with HTG and ACI in European Whites, was not found in either group. Maybe it is not associated with Chinese incidence of HTG and ACI.
4 History of smoking, hypertension and diabetes were independent risk factors for ACI respectively, which is in line with the understanding of the past.
5 The study found no direct correlation between obesity and the incidence of ACI.
方法:对41例动脉粥样硬化性脑梗死患者和88例人群随机挑选对照进行病例对照研究。运用多聚酶链反应-限制性内切酶片段长度多态性(PCR-RFLP)分析技术分别检测LPL基因PvuⅡ及N291S多态性,并测定血清TG含量。分析高血压、糖尿病、高血脂、吸烟、体重指数及LPL基因PvuⅡ及N291S多态性位点与ACI发病的相关性。
结果
1 ACI组与对照组的一般情况:两组人群的年龄和性别比例没有统计学差异。ACI组的BMI高于对照组,但无统计学意义(P>0.05),有吸烟史、糖尿病史和高血压病史者明显多于对照组(P<0.05)。
2两组中PvuⅡ位点基因型均以P+P-型多见,其次为P+P+型,而P-P-型比较少见;其等位基因频率分布均以P+等位基因为常见等位基因,P-等位基因为少见等位基因。两组人群中PvuⅡ多态性基因型分布符合Hardy-Weinberg平衡,具有群体代表性。ACI组和对照组P+P+、P+P-、P-P-基因型频率分别为0.341vs0.295、0.512vs0.534、0.147vs0.171,差异无统计学意义(P>0.05);两组P+、P-等位基因频率分别为0.598 vs0.563、0.402vs0.437,差异亦无统计学意义(P>0.05)。
3 ACI组中P+P+、P+P-、P-P-基因型的血清TG水平逐渐递减(3.50±2.32vs2.75±2.07vs1.88±1.04),但无统计学差异(F=1.44,P=0.2504);对照组中P+P+、P+P-、P-P-基因型的血清TG水平分别为(2.07±0.61vs1.88±0.57vs1.87±0.57),三者比较差异亦无统计学意义(F=1.01,P=0.3672)。
4 ACI组中HTG、NTG亚组P+P+型、P+P-型、P-P-型频率分别为37.0%vs28.6%、55.6%vs42.9%、7.4%vs28.5%,两亚组比较无统计学差异(X2=0.038,P =0.846>0.05),P+、P-等位基因频率分别为64.8%vs50.0%、35.2%vs50.0%,差异亦无统计学意义(P>0.05);对照组中HTG、NTG亚组P+P+型、P+P-型、P-P-型频率分别为22.4%vs38.5%、57.1%vs48.7%、11.5%vs12.8%,两亚组比较无统计学差异(X2=2.907,P = 0.234>0.05),P+、P-等位基因频率分别为51.0%vs62.8%、49.0%vs37.2%,差异亦无统计学意义(P>0.05)。
5以是否患ACI为应变量,高血压、糖尿病、吸烟、携带P+等位基因、肥胖(BMI)等ACI常见危险因素为自变量,进行多因素Logistic回归分析,以a =0.1为入选和排除标准,结果发现吸烟史(OR=3.367)、高血压病史(OR=3.185)、糖尿病病史(OR=3.409)进入模型,是ACI的独立危险因素;而携带P+等位基因则未进入模型,不是ACI的独立危险因素。
6 N291S突变在病对两组中均未发现。
结论
1 LPL基因P+等位基因与血清TG水平无明显相关性。
2 LPL基因P+等位基因与ACI发生不相关,可能不足以构成ACI的独立遗传性危险因子。
3 LPL基因N291S突变在病对两组中均未发现,推测在欧洲白种人存在的与HTG、ACI的发生相关联的LPL常见基因变异N291S可能与中国人HTG、ACI的发生无关。
4吸烟史、高血压史、糖尿病史是ACI的独立危险因素,与以往认识相符。
5本组实验未发现肥胖与ACI发生存在直接相关性。
Objective: Many Researches show that, different gene polymorphisms of Lipoprotein lipase(LPL) have certain effects on blood lipids (especially on triglyceride , TG), while hypertriglyceridemia(HTG) is an important risk factor for atherosclerotic cerebral infarction(ACI). The aim of this study is to investigate the association of PvuⅡand N291S polymorphisms in LPL gene with HTG and ACI.
Methods: The genotype and allele frequencies of LPL gene polymorphisms (PvuⅡand N291S) were analyzed by PCR-restriction fragment length polymorphism in 41 ACI patients and 88 random-selected healthy control individuals. Meanwhile serum triglyceride levels were determined. The correlation of high blood pressure, diabetes, high cholesterol, smoking, body mass index, PvuⅡand N291S gene polymorphisms with the incidence of ACI were also analyzed.
Results
1 The general state of ACI group and the control group: In two groups there was no difference between the age and sex ratio. ACI group of patients have higher body mass index without statistical significance (P>0.05), but Significantly higher smoking rates, prevalence of hypertension and diabetes compared with the control group (P<0.05).
2 In the two groups, P+P- genotype were prevalent, followed by P+P+ and P-P- is relatively rare; P+ is the main allele and P- is the rare allele. The genotype distribution of PvuⅡin both groups corresponds to Hardy-Weinberg equilibrium, with groups’representation. In ACI group and the control group, P+P+、P+P-、P-P- genotype frequencies are 0.341vs0.295, 0.512vs0.534, 0.147vs0.171 respectively, without statistical significance (P>0.05); P+、P- allele frequencies are 0.598vs0.563, 0.402vs0.437 respectively, the differences between the two groups were also without statistically significant (P>0.05).
3 In ACI group, serum triglyceride concentrations of P+P+、P+P-、P-P- genotype are 3.50±2.32vs2.75±2.07vs1.88±1.04 respectively, exhibiting a gradual decrease, but without statistical significance(F=1.44,P=0.2504). In control group, serum triglyceride concentrations of P+P+、P+P-、P-P- genotype are 2.07±0.61vs1.88±0.57vs1.87±0.57 respectively, also without statistically significant differences among the three(F=1.01,P= 0.3672).
4 In HTG and NTG subgroups of ACI group, P+P+、P+P-、P-P- genotype frequencies are 0.370vs0.286, 0.556vs0.429, 0.074vs0.285 respectively, without statistical significance (X2= 0.038,P= 0.846>0.05). P+、P- allele frequencies are 0.648vs 0.500, 0.352vs0.500 respectively, without statistical significance (P>0.05). In HTG and NTG subgroups of the controls, P+P+、P+P-、P-P- genotype frequencies are 0.224vs0.385, 0.571vs 0.487, 0.115vs0.128 respectively, without statistical significance (X2=2.907,P=0.234>0.05). P+、P- allele frequencies are 0.510 vs0.628, 0.490vs0.372, without statistical significance(P>0.05).
5 A multivariate logistic regression analysis, with a =0.1 as the selective and exclusive criterion. The dependent variable was getting the ACI or not and the independent variables included hypertension, diabetes, smoking, carrying P+ allele, obesity(BMI) and other risk factors for ACI. It is found that smoking history, hypertension, diabetes were brought into the model, as independent risk factors for ACI; while carrying P+ allele was not.
6 N291S mutation of LPL was not found in either group.
Conclusion
1 The allele P+ had no significant correlation with serum triglyceride levels.
2 The allele P+, which had no association with ACI, couldn’t be regarded as one of the independent genetic risk factors for ACI in Chinese population.
3 N291S mutation of LPL, which had certain association with HTG and ACI in European Whites, was not found in either group. Maybe it is not associated with Chinese incidence of HTG and ACI.
4 History of smoking, hypertension and diabetes were independent risk factors for ACI respectively, which is in line with the understanding of the past.
5 The study found no direct correlation between obesity and the incidence of ACI.
引文
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1 Hitsumoto T,Yoshinaga K,Aoyagi K,et al. Association between preheparin serum lipoprotein lipase mass and acute myocardial infarction in Japanese men. J Atheroscler Thromb, 2002, 9(4): 163~169
2 Hitsumoto T,Yoshinaga K,Noike H,et al. Clinical significance of preheparin serum lipoprotein lipase mass in coronary vasospasm. Jpn Circ J,2001,65(6): 539~544
3 Tsutsumi K. Lipoprotein lipase and atherosclerosis. Curr Vasc Pharmacol, 2003, 1(1): 11~17
4 Babaev VR , Patel MB , Semenkovich CF , et al. Macrophage lipoprotein lipase promotes foam cell formation and atherosclerosis in low density lipoproteinreceptor-deficient mice. J Biol Chem,2000,275(34):26293~26299
5 Ichikawa T, Liang J, Kitajima S, et al. Macrophage-derived lipoprotein lipase increases aortic atherosclerosis in cholesterol-fed Tg rabbits. Atherosclerosis, 2005,179(1):87~95
6 Wu X, Wang J, Fan J, et al. Localized vessel expression of lipoprotein lipase in rabbits leads to rapid lipid deposition in the balloon-injured arterial wall. Atherosclerosis, 2006, 187(1): 65~73
7 Clee SM,Bissada N,Miao F,et al. Plasma and vessel wall lipoprotein lipase have different roles in atherosclerosis. J Lipid Res,2000,41(4):521~531
8 王绍欣,牟建军,董平栓等. 肥胖高血压患者血清脂蛋白脂酶水平的临床意义及相关性分析. 中国老年学杂志,2004,24(3):211~213
9 Hanyu O, Miida T, Obayashi K, et al. Lipoprotein lipase(LPL) mass in preheparin serum reflects insulin sensitivity. Atherosclerosis, 2004, 174(2): 385~390
10 Hitsumoto T, Ohsawa H, Uchi T, et al. Preheparin serum lipoprotein lipase mass is negatively related to coronary atherosclerosis. Atherosclerosis, 2000, 153(2): 391~396
11 陈忠,马根山,黄峻等. 脂蛋白脂酶活性与早发冠心病临床表型关系的初步探讨. 中国病理生理杂志,2004,20(4):608,626
12 郭朝阳,隋少玉,郭朝晖等. 脂蛋白脂酶活性与老年 2型糖尿病关系的研究. 中国老年学杂志,2004,24(6):510~511
13 钟海新,陈玉驹,严棠等. 2 型糖尿病患者脂蛋白脂酶活性的变化. 广东医学,2002,23(7):698~699
14 阎秀娟,李华,宋国英等. 2 型糖尿病患者脂蛋白脂酶常见变异基因检测. 郑州大学学报(医学版),2005,40(1):38~41
15 Ross CJ, Liu G, Kuivenhoven JA, et al. Complete rescue of lipoprotein lipase-deficient mice by somatic gene transfer of the naturally occurring LPLS447X beneficial mutation. Arterioscler Thromb Vasc Biol, 2005, 25(10): 2143~2150
16 仝其广,赵水平,肖志杰等. 脂蛋白脂酶 Ser447Ter 基因变异对血压影响. 中华心血管病杂志,2004,32(5):474
17 李颖莉,秦勤,崔让庄等. 脂蛋白脂酶基因 S447X 及HindⅢ位点多态性与冠心病的关系. 中国分子心脏病学杂志,2004,4(3):149~154
18 Arai H, Yamamoto A, Matsuzawa Y, et al. Polymophisms in four genes related to triglyceride and HDL-cholesterol levels in the general Japanese population in 2000. J Atheroscler Thromb, 2005, 12(5): 240~250
19 Zhao SP, Tong QG, Xiao ZJ, et al. The lipoprotein lipase Ser447Ter mutation and risk of stroke in the Chinese. Clin Chim Acta. 2003, 330(1~2): 161~164
20 Nierman MC,Prinsen BH, Rip J,et al. Enhanced conversion of triglyceride-rich lipoproteins and increased low-density lipoprotein removal in LPLS447X carriers.Atheroscler Thromb Vasc Biol, 2005, 25: 2410~2415
21 Nierman MC,Rip J,Twisk J,et al. Gene therapy for genetic lipoprotein lipase deficiency:from promise to practice. Neth J Med,2005,63(1):14~19
22 Talmud PJ,Berglund L,Hawe EM,et al. Age-related effects of genetic variation on lipid levels:the Columbia University BioMarkers Study. Pediatrics,2001,108(3):e50
22 Garenc C,Perusse L,Bergeron J,et al. Evidence of LPL gene-exercise interaction for body fat and LPL activity:the HERITAGE Family Study. J Appl Physiol,2001,91(3):1334~1340
24 Baum L, Ng HK, Wong KS, et al. Associations of apolipoprotein E exon 4 and lipoprotein lipase S447X polymorphisms with acute ischemic stroke and myocardial infarction. Clin Chem Lab Med, 2006, 44(3): 274~281
25 Lee J,Tan CS,Chia KS,et al. The lipoprotein lipase S447X polymorphism and plasma lipids:interactions with APOE polymorphisms,smoking,and alcohol consumption. J Lipid Res,2004,45(6):1132~1139
26 Hubacek JA,Waterworth DM,Pitha J,et al. Polymorphi- sms in the lipoprotein lipase and hepatic lipase genes and plasma lipid values in the Czech population. Physiol Res,2001,50(4):345~351
27 Fidani L, Hatzitolios AI, Goulas A, et al. Cholesteryl ester transfer protein Taq Ⅰ B and lipoprotein lipase Ser447Tergene polymorphisms are not associated with ischemic stroke in Greek patients. Neurosci Lett, 2005, 384(1~2): 102~105
28 王成,白悦心,欧阳安. 糖原合成酶和脂蛋白脂酶基因多态性与糖尿病及其心血管并发症的关系. 中华医学杂志,2000,80(3):178~179
29 李蓉,李启富,郭立新等. 单纯性肥胖患者脂蛋白脂酶基因多态性. 中华内分泌代谢杂志,2003,19(3):225~227
30 张蓉,樊云,刘宇等. 2 型糖尿病与脂蛋白脂酶基因HindⅢ酶切位点的多态性. 基础医学与临床,2004,24(2):141~144
31 Taylor KD, Scheuner MT, Yang H, et al. Lipoprotein lipase locus and progression of atherosclerosis in coronary- artery bypass grafts. Genet Med, 2004, 6(6): 481~486
32 冯霞,周新,刘芳等. 冠心病患者脂蛋白脂酶基因 HindⅢ多态性及与血脂的关系. 武汉大学学报(医学版),2004,25(2):209~212
33 陈忠,黄峻,朱铁兵等. 早发冠心病患者脂蛋白脂酶基因多态性与血脂关系研究. 临床心血管病杂志,2002,18(10):487~489
34 Socquard E, Durlach A, Clavel C, et al. Association of Hind Ⅲ and Pvu Ⅱ genetic polymorphisms of lipoprotein lipase with lipid metabolism and macrovascular events in type 2 diabetic patients. Diabetes Metab, 2006, 32(3): 262~269
35 朱文丽,齐智,张震涛等. 北京市城区中老年人群脂蛋白脂酶基因变异与肥胖代谢综合征的关系. 中国慢性病预防与控制,2002,10(5):210~212,240
36 樊芸,张蓉,张祖辉. Ⅱ型糖尿病与脂蛋白脂酶基因PvuⅡ多态性的关联. 四川生理科学杂志,2001,23(2):76~78
37 朱文丽,齐智,张震涛等. 北京市西城区中老年人群脂蛋白脂酶基因多态性与高脂血症关系的研究. 中华医学遗传学杂志,2002,19(4):361~362
38 苏慧,李兰荪,贾国良. LPL 基因多态性与血浆 TG 水平及冠脉病变严重度的关系. 第四军医大学学报,2001,22(21):1992~1995
39 崔翰斌,崔长琮,马奕等. 高密度脂蛋白代谢相关基因单核苷酸多态性研究. 中华医学遗传学杂志,2005,22(1):22~26
40 Larson I,Hoffmann MM,Ordovas JM,et al. The Lipoprotein lipase Hind Ⅲ polymorphism:association with total cholesterol and LDL-Cholesterol,but not with HDL and triglycerides in 342 females. Clin Chem,1999,45(7):963~968
41 Shen H, Yu S,Xu Y, et al. DNA polymorphism of Pvu Ⅱ site in the lipoprotein lipase gene in patients with type 2 diabetes mellitus. Zhonghua Yi Xue Yi Chuan Xue Za Zhi, 2000, 17(1): 24~27
42 Lopez-Miranda J,Cruz G,Gomez P,et al. The influence of lipoprotein lipase gene variation on postprandiallipoprotein metabolism. J Clin Endocrinol Metab,2004,89(9):4721~4728
43 刘爱萍,李立明,曹卫华等. 脂蛋白脂酶S447X及HindⅢ多态性与原发性高血压代谢综合征血脂异常的关系. 中华医学遗传学杂志,2005,22(2):151~157
44 Shimo-Nakanishi Y , Urabe T , Hattori N , et al. Polymorphism of the lipoprotein lipase gene and risk of atherothrombotic cerebral infarction in the Japanese. Stroke,2001,32(7): 1481~1486
45 毛霞,马沛然,牛峰海等. 小儿单纯性肥胖脂蛋白脂酶基因的多态性研究. 临床儿科杂志,2000,18(5):259~261
46 Wittrup HH,Nordestgaard BG,Sillesen H,et al. A common mutation in lipoprotein lipase confers a 2-fold increase in risk of ischemic cerebrovascular disease in women but not in men. Circulation,2000,101(20):2393~2397
47 Ordovas JM. Lipoprotein lipase genetic variation and gender-specific ischemic cerebrovascular disease risk. Nutr Rev. 2000, 58(10): 315~318
48 Brousseau ME , Goldkamp AL , Collins D , et al. Polymorphisms in the gene encoding lipoprotein lipase in men with low HDL-C and coronary heart disease:The Veterans Affairs HDL Intervention Trial. J Lipid Res,2004,45(10):1885~1891
49 Yang Y, Ruiz-Narvaez E, Niu T, et al. Genetic variants of the lipoprotein lipase gene and myocardial infarction in theCentral Valley of Costa Rita. J Lipid Res, 2004, 45(11): 2106~2109
50 Arca M, Campagna F, Montali A, et al. The common mutations in the lipoprotein lipase gene in Italy: effects on plasma lipids and angiographically assessed coronary atherosclerosis. Clin Genet, 2000, 58(5): 369~374
51 Spence JD, Ban MR, Hegele RA. Lipoprotein lipase (LPL) gene variation and progression of carotid artery plaque. Stroke,2003,34(5): 1176~1180
52 赵迎社,周羽并,林春兰等. 中国人混合型高脂血症患者脂蛋白脂酶常见基因变异的筛查. 广东医学,2001,22(5):381~382
53 Wittrup HH,Tybjaerg-Hansen A,Nordestgaard BG,et al. Lipoprotein lipase mutations , plasma lipids and lipoproteins , and risk of ischemic heart disease. A meta-analysis. Circulation,1999,99(22):2901~2907
54 Li B,Ge DL,Wang YL,et al. Lipoprotein lipase gene polymorphisms and blood pressure levels in the Northern Chinese Han Population. Hypertens Res,2004,27(6):373~378
55 杨文杰,顾东风,葛东亮等. LPL 基因旁侧区域内多态性与高血压病或血压数量性状的连锁分析. 中华心血管病杂志,2004,32(9):777~780
56 Yang WJ,Huang JF,Ge DL,et al. Variation near the region of the lipoprotein lipase gene and hypertension or blood pressure levels in Chinese. Hypertens Res,2003,26(6):459~464
57 Yang WJ,Huang JF,Yao CL,et al. Evidence for linkage and association of the markers near the LPL gene with hypertension in Chinese families. J Med Genet,2003,40(5):e57
58 Ruel IL,Gaudet D,Perron P,et al. Characterization of LDL particle size among carriers of a defective or a null mutation in the lipoprotein lipase gene:the Quebec LIPD Study. Arterioscler Thromb Vasc Biol,2002,22(7):1181~1186
59 Peterson J,Ayyobi AF,Ma YH,et al. Structure and functional consequences of missense mutations in exon 5 of the lipoprotein lipase gene. J Lipid Res,2002,43(3):398~406
2 Hitsumoto T,Yoshinaga K,Noike H,et al. Clinical significance of preheparin serum lipoprotein lipase mass in coronary vasospasm. Jpn Circ J,2001,65(6): 539~544
3 Tsutsumi K. Lipoprotein lipase and atherosclerosis. Curr Vasc Pharmacol, 2003, 1(1): 11~17
4 Babaev VR , Patel MB , Semenkovich CF , et al. Macrophage lipoprotein lipase promotes foam cell formation and atherosclerosis in low density lipoprotein receptor-deficient mice. J Biol Chem,2000,275(34):26293~26299
5 Babaev VR,Fazio S,Gleaves LA,et al. Macrophage lipoprotein lipase promotes foam cell formation and atherosclerosis in vivo. J Clin Invest,1999,103(12):1697~1705
6 Wu X, Wang J, Fan J, et al. Localized vessel expression of lipoprotein lipase in rabbits leads to rapid lipid deposition in the balloon-injured arterial wall. Atherosclerosis, 2006, 187(1): 65~73
7 Clee SM,Bissada N,Miao F,et al. Plasma and vessel wall lipoprotein lipase have different roles in atherosclerosis.J Lipid Res,2000,41(4):521~531
8 Ahn YI, Kamboh MI, Hamman RF, et al. Two DNA polymorphisms in the lipoprotein lipase gene and theirassociations with factors related to cardiovascular disease.J Lipid Res, 1993, 34(3): 421~428
9 Gerdes C, Gerdes LU, Hansen PS, et al. Polymorphisms in the lipoprotein lipase gene and their association with plasma lipid concentration in 40-year-old Danish men[J]. Circulation, 1995, 92(7): 1765~1769
10 Shimo-Nakanishi Y,Urabe T, Hattori N,et al. Polymorphism of the lipoprotein lipase gene and risk of atherothrombotic cerebral infarction in the Japanese. Stroke, 2001, 32(7): 1481~1486
11 樊芸,张蓉,张祖辉. Ⅱ型糖尿病与脂蛋白脂酶基因PvuⅡ多态性的关联. 四川生理科学杂志,2001,23(2):76~78
12 Yin R, Wang Y, Chen G, et al. Lipoprotein lipase gene polymorphism at the Pvu Ⅱ locus and serum lipid levels in Guangxi Hei Yi Zhuang and Han population. Clin Chem Lab Med, 2006, 44(12): 1416~1421
13 崔翰斌,崔长琮,马奕等. 高密度脂蛋白代谢相关基因单核苷酸多态性研究. 中华医学遗传学杂志,2005,22(1):22~26
14 朱文丽,齐智,张震涛等. 北京市西城区中老年人群脂蛋白脂酶基因多态性与高脂血症关系的研究. 中华医学遗传学杂志,2002,19(4):361~362
15 陈忠,黄峻,朱铁兵等. 早发冠心病患者脂蛋白脂酶基因多态性与血脂关系研究. 临床心血管病杂志,2002,18(10):487~489
16 Pasalic D, Sertic J, Kunovic B, et al. Lipoprotein lipase gene polymorphism and lipid profile in patients with hypertriglyceridemia. Croatian Medical Journal, 2001, 42(5):517~522
17 苏慧, 李兰荪, 贾国良. LPL 基因多态性与血浆 TG 水平及冠脉病变严重度的关系. 第四军医大学学报, 2001, 22(21):1992~1995
18 向光大,王颖群,夏邦顺等. 2 型糖尿病患者脂蛋白脂酶基因多态性与冠心病关系的研究. 中华内分泌代谢杂志,2001,17(6):368~369
19 Brousseau ME,Goldkamp AL,Collins D,et al. Polymorphi- sms in the gene encoding lipoprotein lipase in men withlow HDL-C and coronary heart disease:The Veterans Affairs HDL Intervention Trial. J Lipid Res,2004,45(10):1885~1891
20 Yang Y, Ruiz-Narvaez E, Niu T, et al. Genetic variants of the lipoprotein lipase gene and myocardial infarction in the Central Valley of Costa Rita. J Lipid Res, 2004, 45(11): 2106~2109
21 Wittrup HH,Tybjaerg-Hansen A,Nordestgaard BG,et al. Lipoprotein lipase mutations , plasma lipids and lipoproteins , and risk of ischemic heart disease. A meta-analysis. Circulation,1999,99(22):2901~2907
22 赵迎社,周羽并,林春兰等. 中国人混合型高脂血症患者脂蛋白脂酶常见基因变异的筛查. 广东医学,2001,22(5):381~382
23 阎秀娟,李华,宋国英等. 2 型糖尿病患者脂蛋白脂酶常见变异基因检测. 郑州大学学报(医学版),2005,40(1):38~41
24 张秋萍,刘秉文,刘宇等. 中国人内源性高甘油三酯血症患者脂蛋白脂酶及肝脂酶常见基因变异的研究. 中华医学遗传学杂志,1997,14(5):289~293
1 Hitsumoto T,Yoshinaga K,Aoyagi K,et al. Association between preheparin serum lipoprotein lipase mass and acute myocardial infarction in Japanese men. J Atheroscler Thromb, 2002, 9(4): 163~169
2 Hitsumoto T,Yoshinaga K,Noike H,et al. Clinical significance of preheparin serum lipoprotein lipase mass in coronary vasospasm. Jpn Circ J,2001,65(6): 539~544
3 Tsutsumi K. Lipoprotein lipase and atherosclerosis. Curr Vasc Pharmacol, 2003, 1(1): 11~17
4 Babaev VR , Patel MB , Semenkovich CF , et al. Macrophage lipoprotein lipase promotes foam cell formation and atherosclerosis in low density lipoproteinreceptor-deficient mice. J Biol Chem,2000,275(34):26293~26299
5 Ichikawa T, Liang J, Kitajima S, et al. Macrophage-derived lipoprotein lipase increases aortic atherosclerosis in cholesterol-fed Tg rabbits. Atherosclerosis, 2005,179(1):87~95
6 Wu X, Wang J, Fan J, et al. Localized vessel expression of lipoprotein lipase in rabbits leads to rapid lipid deposition in the balloon-injured arterial wall. Atherosclerosis, 2006, 187(1): 65~73
7 Clee SM,Bissada N,Miao F,et al. Plasma and vessel wall lipoprotein lipase have different roles in atherosclerosis. J Lipid Res,2000,41(4):521~531
8 王绍欣,牟建军,董平栓等. 肥胖高血压患者血清脂蛋白脂酶水平的临床意义及相关性分析. 中国老年学杂志,2004,24(3):211~213
9 Hanyu O, Miida T, Obayashi K, et al. Lipoprotein lipase(LPL) mass in preheparin serum reflects insulin sensitivity. Atherosclerosis, 2004, 174(2): 385~390
10 Hitsumoto T, Ohsawa H, Uchi T, et al. Preheparin serum lipoprotein lipase mass is negatively related to coronary atherosclerosis. Atherosclerosis, 2000, 153(2): 391~396
11 陈忠,马根山,黄峻等. 脂蛋白脂酶活性与早发冠心病临床表型关系的初步探讨. 中国病理生理杂志,2004,20(4):608,626
12 郭朝阳,隋少玉,郭朝晖等. 脂蛋白脂酶活性与老年 2型糖尿病关系的研究. 中国老年学杂志,2004,24(6):510~511
13 钟海新,陈玉驹,严棠等. 2 型糖尿病患者脂蛋白脂酶活性的变化. 广东医学,2002,23(7):698~699
14 阎秀娟,李华,宋国英等. 2 型糖尿病患者脂蛋白脂酶常见变异基因检测. 郑州大学学报(医学版),2005,40(1):38~41
15 Ross CJ, Liu G, Kuivenhoven JA, et al. Complete rescue of lipoprotein lipase-deficient mice by somatic gene transfer of the naturally occurring LPLS447X beneficial mutation. Arterioscler Thromb Vasc Biol, 2005, 25(10): 2143~2150
16 仝其广,赵水平,肖志杰等. 脂蛋白脂酶 Ser447Ter 基因变异对血压影响. 中华心血管病杂志,2004,32(5):474
17 李颖莉,秦勤,崔让庄等. 脂蛋白脂酶基因 S447X 及HindⅢ位点多态性与冠心病的关系. 中国分子心脏病学杂志,2004,4(3):149~154
18 Arai H, Yamamoto A, Matsuzawa Y, et al. Polymophisms in four genes related to triglyceride and HDL-cholesterol levels in the general Japanese population in 2000. J Atheroscler Thromb, 2005, 12(5): 240~250
19 Zhao SP, Tong QG, Xiao ZJ, et al. The lipoprotein lipase Ser447Ter mutation and risk of stroke in the Chinese. Clin Chim Acta. 2003, 330(1~2): 161~164
20 Nierman MC,Prinsen BH, Rip J,et al. Enhanced conversion of triglyceride-rich lipoproteins and increased low-density lipoprotein removal in LPLS447X carriers.Atheroscler Thromb Vasc Biol, 2005, 25: 2410~2415
21 Nierman MC,Rip J,Twisk J,et al. Gene therapy for genetic lipoprotein lipase deficiency:from promise to practice. Neth J Med,2005,63(1):14~19
22 Talmud PJ,Berglund L,Hawe EM,et al. Age-related effects of genetic variation on lipid levels:the Columbia University BioMarkers Study. Pediatrics,2001,108(3):e50
22 Garenc C,Perusse L,Bergeron J,et al. Evidence of LPL gene-exercise interaction for body fat and LPL activity:the HERITAGE Family Study. J Appl Physiol,2001,91(3):1334~1340
24 Baum L, Ng HK, Wong KS, et al. Associations of apolipoprotein E exon 4 and lipoprotein lipase S447X polymorphisms with acute ischemic stroke and myocardial infarction. Clin Chem Lab Med, 2006, 44(3): 274~281
25 Lee J,Tan CS,Chia KS,et al. The lipoprotein lipase S447X polymorphism and plasma lipids:interactions with APOE polymorphisms,smoking,and alcohol consumption. J Lipid Res,2004,45(6):1132~1139
26 Hubacek JA,Waterworth DM,Pitha J,et al. Polymorphi- sms in the lipoprotein lipase and hepatic lipase genes and plasma lipid values in the Czech population. Physiol Res,2001,50(4):345~351
27 Fidani L, Hatzitolios AI, Goulas A, et al. Cholesteryl ester transfer protein Taq Ⅰ B and lipoprotein lipase Ser447Tergene polymorphisms are not associated with ischemic stroke in Greek patients. Neurosci Lett, 2005, 384(1~2): 102~105
28 王成,白悦心,欧阳安. 糖原合成酶和脂蛋白脂酶基因多态性与糖尿病及其心血管并发症的关系. 中华医学杂志,2000,80(3):178~179
29 李蓉,李启富,郭立新等. 单纯性肥胖患者脂蛋白脂酶基因多态性. 中华内分泌代谢杂志,2003,19(3):225~227
30 张蓉,樊云,刘宇等. 2 型糖尿病与脂蛋白脂酶基因HindⅢ酶切位点的多态性. 基础医学与临床,2004,24(2):141~144
31 Taylor KD, Scheuner MT, Yang H, et al. Lipoprotein lipase locus and progression of atherosclerosis in coronary- artery bypass grafts. Genet Med, 2004, 6(6): 481~486
32 冯霞,周新,刘芳等. 冠心病患者脂蛋白脂酶基因 HindⅢ多态性及与血脂的关系. 武汉大学学报(医学版),2004,25(2):209~212
33 陈忠,黄峻,朱铁兵等. 早发冠心病患者脂蛋白脂酶基因多态性与血脂关系研究. 临床心血管病杂志,2002,18(10):487~489
34 Socquard E, Durlach A, Clavel C, et al. Association of Hind Ⅲ and Pvu Ⅱ genetic polymorphisms of lipoprotein lipase with lipid metabolism and macrovascular events in type 2 diabetic patients. Diabetes Metab, 2006, 32(3): 262~269
35 朱文丽,齐智,张震涛等. 北京市城区中老年人群脂蛋白脂酶基因变异与肥胖代谢综合征的关系. 中国慢性病预防与控制,2002,10(5):210~212,240
36 樊芸,张蓉,张祖辉. Ⅱ型糖尿病与脂蛋白脂酶基因PvuⅡ多态性的关联. 四川生理科学杂志,2001,23(2):76~78
37 朱文丽,齐智,张震涛等. 北京市西城区中老年人群脂蛋白脂酶基因多态性与高脂血症关系的研究. 中华医学遗传学杂志,2002,19(4):361~362
38 苏慧,李兰荪,贾国良. LPL 基因多态性与血浆 TG 水平及冠脉病变严重度的关系. 第四军医大学学报,2001,22(21):1992~1995
39 崔翰斌,崔长琮,马奕等. 高密度脂蛋白代谢相关基因单核苷酸多态性研究. 中华医学遗传学杂志,2005,22(1):22~26
40 Larson I,Hoffmann MM,Ordovas JM,et al. The Lipoprotein lipase Hind Ⅲ polymorphism:association with total cholesterol and LDL-Cholesterol,but not with HDL and triglycerides in 342 females. Clin Chem,1999,45(7):963~968
41 Shen H, Yu S,Xu Y, et al. DNA polymorphism of Pvu Ⅱ site in the lipoprotein lipase gene in patients with type 2 diabetes mellitus. Zhonghua Yi Xue Yi Chuan Xue Za Zhi, 2000, 17(1): 24~27
42 Lopez-Miranda J,Cruz G,Gomez P,et al. The influence of lipoprotein lipase gene variation on postprandiallipoprotein metabolism. J Clin Endocrinol Metab,2004,89(9):4721~4728
43 刘爱萍,李立明,曹卫华等. 脂蛋白脂酶S447X及HindⅢ多态性与原发性高血压代谢综合征血脂异常的关系. 中华医学遗传学杂志,2005,22(2):151~157
44 Shimo-Nakanishi Y , Urabe T , Hattori N , et al. Polymorphism of the lipoprotein lipase gene and risk of atherothrombotic cerebral infarction in the Japanese. Stroke,2001,32(7): 1481~1486
45 毛霞,马沛然,牛峰海等. 小儿单纯性肥胖脂蛋白脂酶基因的多态性研究. 临床儿科杂志,2000,18(5):259~261
46 Wittrup HH,Nordestgaard BG,Sillesen H,et al. A common mutation in lipoprotein lipase confers a 2-fold increase in risk of ischemic cerebrovascular disease in women but not in men. Circulation,2000,101(20):2393~2397
47 Ordovas JM. Lipoprotein lipase genetic variation and gender-specific ischemic cerebrovascular disease risk. Nutr Rev. 2000, 58(10): 315~318
48 Brousseau ME , Goldkamp AL , Collins D , et al. Polymorphisms in the gene encoding lipoprotein lipase in men with low HDL-C and coronary heart disease:The Veterans Affairs HDL Intervention Trial. J Lipid Res,2004,45(10):1885~1891
49 Yang Y, Ruiz-Narvaez E, Niu T, et al. Genetic variants of the lipoprotein lipase gene and myocardial infarction in theCentral Valley of Costa Rita. J Lipid Res, 2004, 45(11): 2106~2109
50 Arca M, Campagna F, Montali A, et al. The common mutations in the lipoprotein lipase gene in Italy: effects on plasma lipids and angiographically assessed coronary atherosclerosis. Clin Genet, 2000, 58(5): 369~374
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