环氧化酶1、P2Y1、GPⅠa 及 GPⅢa 基因多态性与阿司匹林抵抗的相关性研究

摘要

目的：探讨环氧化酶1（COX -1）（ A842G、C50T）、P2Y1（ A1622G、C893T）、GPⅠ a（ C807T、G873A）及 GPⅢa（T1565C）4个基因中7个位点的多态性与阿司匹林（ ASP）抵抗（AR）的相关性。方法选取2011年10月—2013年12月武警浙江省总队杭州医院内科住院的动脉粥样硬化患者243例，测定患者血小板聚集（PA）率，并将患者分为 AR 组，ASP 半抵抗（ASR）组，ASP 敏感（AS）组。测定各组COX -1、P2Y1、GPⅠa 及GPⅢa 基因型。比较3组患者一般资料及COX -1、P2Y1、GPⅠa、GPⅢa 基因多态性。结果 AR 组28例，ASR 组71例，AS 组144例。3组患者的年龄、性别、吸烟率、高血压发生率、总胆固醇、三酰甘油和低密度脂蛋白水平比较，差异无统计学意义（P >0.05）。3组患者糖尿病发生率比较，差异有统计学意义（ P <0.01）；AS 组患者糖尿病发生率低于 AR 组（ P <0.05）。3组间 COX -1（842 A > G）、COX -1（50 C > T）、P2Y1（1622 A > G）、GP Ⅰ a （873 G > A）、GPⅢa（1565 T > C）频率比较，差异无统计学意义（P >0.05）。3组间 P2Y1（893 C > T）和 GPⅠa （807 C > T）频率比较，差异有统计学意义（P <0.05）；AR 组和 ASR 组 P2Y1（893 C > T）、GPⅠa（807 C > T）频率高于 AS 组（P <0.01）。结论 P2Y1（C893T）、GPⅠa（C807T）等位基因的变异与 AR 具有一定程度的关联，为指导临床用药提供了参考依据。%Objectjve To investigate the correlation between polymorphisms of 7 sites in 4 genes COX - 1(A842G, C50T),P2Y1(A1622G,C893T),GPⅠa(C807T,G873A)and GPⅢa(T1565C)and aspirin resistance(AR). Methods A total of 243 patients with atherosclerosis who were admitted to Department of Internal Medicine in Zhejiang Armed Police Corps Hangzhou Hospital during October 2011 to December 2013,were selected as study subjects,the platelet agglutination rate was detected,patients were divided into three groups:aspirin resistant(AR)group,aspirin semi - responder(ASR)group and aspirin sensitive( AS) group,genotype of COX - 1,P2Y1,GP Ⅰ a and GP Ⅲ a was analyzed respectively. The general informations and gene polymorphisms of COX - 1, P2Y1, GP Ⅰ a, GP Ⅲ a were compared among three groups of patients. Results AR group,ASR group and AS group included 28 cases,71 cases and 144 cases,respectively. There was no significant difference in age,gender,smoking rate,hypertension prevalence,total cholesterol level,triacylglycerol level and low density lipoprotein level among three groups of patients(P > 0. 05). There was significant difference in prevalence of diabetes mellitus among three groups of patients( P < 0. 01). Prevalence of diabetes mellitus of patients in AS group was significantly lower than that of patients in AR group(P < 0. 05). There was no significant difference in frequency of COX - 1(842 A > G), COX - 1(50 C > T),P2Y1(1622 A > G),GPⅠa(873 G > A)and GPⅢa(1565 T > C)among three groups(P > 0. 05). There were significant differences in frequency of P2Y1(893 C > T)and GPⅠa(807 C > T)among three groups(P < 0. 05), and the frequency of P2Y1(893 C > T)and GPⅠa(807 C > T)in AR group and ASR group was significantly higher than that in AS group,respectively( P < 0. 01). Conclusjon There are correlations between mutation of P2Y1( C893T),GPⅠ a (C807T)alleles and aspirin resistance,which provides a reference for guiding the clinical medication.