PEAR1基因多态性与缺血性脑卒中患者阿司匹林反应相关性研究
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摘要
目的探讨缺血性脑卒中患者阿司匹林反应与血小板内皮聚集受体1(platelet endothelial aggregation receptor1,PEAR1)基因多态性的相关性。方法对148例缺血性脑卒中患者给予阿司匹林100 mg/日,连续服用7 d后,进行血栓弹力图检测,根据结果分为对照组(即阿司匹林敏感患者,102例)和观察组(即阿司匹林抵抗患者,46例)。比较两组患者的一般临床资料,并采用荧光染色体原位杂交技术对PEAR1基因型进行检测。采用多因素回归分析单因素分析中存在统计学差异的影响因素与阿司匹林抵抗的关系。结果一般临床资料比较中,发现观察组的性别、饮酒、高密度脂蛋白胆固醇(HDL-C)与对照组的差异有统计学意义(P<0.05);观察组与照组PEAR1基因rs12041331位点基因型分布差异有统计学意义(P<0.05),rs2768759位点两组基因型分布差异无统计学意义(P>0.05);多因素回归分析发现,性别、HDL-C和PEAR1基因rs12041331位点(GA+AA)是阿司匹林抵抗独立危险因素(P<0.05)。结论 PEAR1基因rs12041331位点A等位基因与缺血性脑卒中患者阿司匹林抵抗的发生有关。
Objective To investigate the relationship between platelet endothelial aggregation receptor 1(PEAR1) gene polymorphism and aspirin response in patients with ischemic stroke. Methods 148 patients with ischemic stroke were included. After 7 days of continuous administration, 100 mg per day, the thromboelastography was performed, and the patients were divided into the control group(aspirin sensitive patients, 102 cases) and the observation group(aspirin resistance patients, 46 cases) according to the results. The general clinical data of the two groups were compared, and the PEAR1 genotypes were detected by fluorescence in situ hybridization(FISH). Multivariate regression analysis was used to analyze the relationship between influencing factors with statistical differences in single factor analysis and aspirin resistance. Results In the comparison of general clinical data, there were significant differences in gender, drinking, and HDL-C between the observation group and the control group(P<0.05). There was significant difference in the genotype distribution the PEAR1 gene rs12041331 locus between the observation group and the control group(P<0.05). There was no significant difference in the genotype distribution of rs2768759 locus between the two groups(P>0.05). Multivariate regression analysis showed that gender, HDL-C and PEAR1 gene rs12041331 locus(GA+AA) were independent risk factors for aspirin resistance(P<0.05). Conclusion The A allele at the rs12041331 locus of PEAR1 gene is associated with the occurrence of aspirin resistance in ischemic stroke patients.
Objective To investigate the relationship between platelet endothelial aggregation receptor 1(PEAR1) gene polymorphism and aspirin response in patients with ischemic stroke. Methods 148 patients with ischemic stroke were included. After 7 days of continuous administration, 100 mg per day, the thromboelastography was performed, and the patients were divided into the control group(aspirin sensitive patients, 102 cases) and the observation group(aspirin resistance patients, 46 cases) according to the results. The general clinical data of the two groups were compared, and the PEAR1 genotypes were detected by fluorescence in situ hybridization(FISH). Multivariate regression analysis was used to analyze the relationship between influencing factors with statistical differences in single factor analysis and aspirin resistance. Results In the comparison of general clinical data, there were significant differences in gender, drinking, and HDL-C between the observation group and the control group(P<0.05). There was significant difference in the genotype distribution the PEAR1 gene rs12041331 locus between the observation group and the control group(P<0.05). There was no significant difference in the genotype distribution of rs2768759 locus between the two groups(P>0.05). Multivariate regression analysis showed that gender, HDL-C and PEAR1 gene rs12041331 locus(GA+AA) were independent risk factors for aspirin resistance(P<0.05). Conclusion The A allele at the rs12041331 locus of PEAR1 gene is associated with the occurrence of aspirin resistance in ischemic stroke patients.
引文
[1]曾洁,柳青,林爱华.广州市社区中老年人群缺血性脑卒中影响因素分析及发病风险预测[J].中山大学学报(医学科学版),2016,37(4):614-620.
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[3]王召月,王雁,隋爱华,等.多药物耐药基因多态性与缺血性脑卒中患者阿司匹林抵抗的相关性[J].中华医学杂志,2016,96(47):3819-3824.
[4]彭玲玲,彭海莹,林伟斌,等.遗传因素与缺血性脑卒中患者发生阿司匹林非敏感的相关性研究进展[J].中国临床药理学杂志,2016,32(10):941-944.
[5]Xiang Q,Zhou S,Lewis J P,et al.Genetic Variants of PEAR1 are associated with platelet function and antiplatelet drug efficacy:a systematic review and meta-analysis[J].Curr Pharm Design,2017,23(44):6815-6827.
[6]李钊,董梅,李世平,等.缺血性脑卒中复发与阿司匹林抵抗的相关性研究[J].中风与神经疾病杂志,2017,34(6):497-499.
[7]彭文绣,陈健华,梅丹,等.阿司匹林抵抗的研究现状及工作启示[J].中国药学杂志,2017,52(14):1285-1290.
[8]Nie X,Li J,Qin S,et al.Genetic mutations in PEAR1 associated with cardiovascular outcomes in Chinese patients with acute coronary syndrome[J].Thromb Res,2018,163:77-82.
[9]Backman J D,Yerges‐Armstrong L M,Horenstein R B,et al.Prospective evaluation of genetic variation in platelet endothelial aggregation receptor 1 reveals aspirin-dependent effects on platelet aggregation pathways[J].Clin Transl Sci,2017,10(2):102-109.
[10]Yang W Y,Petit T,Cauwenberghs N,et al.PEAR1 is not a major susceptibility gene for cardiovascular disease in a Flemish population[J].BMC Med Genet,2017,18(1):45-53.
[11]Li M,Hu Y,Wen Z,et al.Association of PEAR1 rs12041331polymorphism and pharmacodynamics of ticagrelor in healthy Chinese volunteers[J].Xenobiotica,2017,47(12):1130-1138.
[12]Keramati A R,Yanek L R,Iyer K,et al.Targeted deep sequencing of the PEAR1 locus for platelet aggregation in European and African American families[J].Platelets,2018,30(3):1-7.
[13]Van Sloten T T,Sigurdsson S,van Buchem M A,et al.Cerebral small vessel disease and association with higher incidence of depressive symptoms in a general elderly population:the AGES-Reykjavik study[J].Am J Psychiatry,2015,172(6):570-578.
[14]Izzi B,Noro F,Cludts K,et al.Cell-specific PEAR1 methylation studies reveal a locus that coordinates expression of multiple genes[J].Int J Mol Sci,2018,19(4):1069.
[15]邢晓清,卜修民,初亚男,等.焦磷酸测序技术对阿司匹林个体化用药相关SNP位点分型[J].中国药科大学学报,2017,48(5):577-582.
[16]Oladosu F A,Tu F F,Hellman K M.Nonsteroidal antiinflammatory drug resistance in dysmenorrhea:epidemiology,causes,and treatment[J].Am J Obstet Gynecol,2018,218(4):390-400.
[17]范雪松,王恩世,贺建勋,等.冠心病患者尿miR-126的表达及其与阿司匹林抵抗的关系[J].临床检验杂志,2016,34(1):35-37.
[2]涂雪松.缺血性脑卒中的流行病学研究[J].中国临床神经科学,2016,24(5):594-599.
[3]王召月,王雁,隋爱华,等.多药物耐药基因多态性与缺血性脑卒中患者阿司匹林抵抗的相关性[J].中华医学杂志,2016,96(47):3819-3824.
[4]彭玲玲,彭海莹,林伟斌,等.遗传因素与缺血性脑卒中患者发生阿司匹林非敏感的相关性研究进展[J].中国临床药理学杂志,2016,32(10):941-944.
[5]Xiang Q,Zhou S,Lewis J P,et al.Genetic Variants of PEAR1 are associated with platelet function and antiplatelet drug efficacy:a systematic review and meta-analysis[J].Curr Pharm Design,2017,23(44):6815-6827.
[6]李钊,董梅,李世平,等.缺血性脑卒中复发与阿司匹林抵抗的相关性研究[J].中风与神经疾病杂志,2017,34(6):497-499.
[7]彭文绣,陈健华,梅丹,等.阿司匹林抵抗的研究现状及工作启示[J].中国药学杂志,2017,52(14):1285-1290.
[8]Nie X,Li J,Qin S,et al.Genetic mutations in PEAR1 associated with cardiovascular outcomes in Chinese patients with acute coronary syndrome[J].Thromb Res,2018,163:77-82.
[9]Backman J D,Yerges‐Armstrong L M,Horenstein R B,et al.Prospective evaluation of genetic variation in platelet endothelial aggregation receptor 1 reveals aspirin-dependent effects on platelet aggregation pathways[J].Clin Transl Sci,2017,10(2):102-109.
[10]Yang W Y,Petit T,Cauwenberghs N,et al.PEAR1 is not a major susceptibility gene for cardiovascular disease in a Flemish population[J].BMC Med Genet,2017,18(1):45-53.
[11]Li M,Hu Y,Wen Z,et al.Association of PEAR1 rs12041331polymorphism and pharmacodynamics of ticagrelor in healthy Chinese volunteers[J].Xenobiotica,2017,47(12):1130-1138.
[12]Keramati A R,Yanek L R,Iyer K,et al.Targeted deep sequencing of the PEAR1 locus for platelet aggregation in European and African American families[J].Platelets,2018,30(3):1-7.
[13]Van Sloten T T,Sigurdsson S,van Buchem M A,et al.Cerebral small vessel disease and association with higher incidence of depressive symptoms in a general elderly population:the AGES-Reykjavik study[J].Am J Psychiatry,2015,172(6):570-578.
[14]Izzi B,Noro F,Cludts K,et al.Cell-specific PEAR1 methylation studies reveal a locus that coordinates expression of multiple genes[J].Int J Mol Sci,2018,19(4):1069.
[15]邢晓清,卜修民,初亚男,等.焦磷酸测序技术对阿司匹林个体化用药相关SNP位点分型[J].中国药科大学学报,2017,48(5):577-582.
[16]Oladosu F A,Tu F F,Hellman K M.Nonsteroidal antiinflammatory drug resistance in dysmenorrhea:epidemiology,causes,and treatment[J].Am J Obstet Gynecol,2018,218(4):390-400.
[17]范雪松,王恩世,贺建勋,等.冠心病患者尿miR-126的表达及其与阿司匹林抵抗的关系[J].临床检验杂志,2016,34(1):35-37.