阿司匹林抵抗与环氧化酶-1、环氧化酶-2及血栓烷A2受体基因多态性相关性研究  

Correlation Study Between Aspirin Resistance and COX1, COX2, TBXA2R Gene Polymorphisms in Patients With Coronary Artery Disease

作　　者：许晶晶[1] 唐晓芳[1] 姚懿[1] 徐娜[1] 张佳慧[1] 马元良[1] 宋莹[1] 袁晋青[1] 

机构地区：[1]中国医学科学院北京协和医学院国家心血管病中心阜外医院心内科,北京市100037

出　　处：《中国循环杂志》2016年第7期644-648,共5页Chinese Circulation Journal

基　　金：国家自然科学基金资助项目(81470486)

摘　　要：目的:探讨冠心病二级预防中的阿司匹林抵抗现象,及其与环氧化酶-1(COX1)、环氧化酶-2(COX2)、血栓烷A2受体(TBXA2R)基因多态性之间相关性。方法:选取连续服用阿司匹林100 mg大于7天的冠心病患者2 881例,选择符合阿司匹林抵抗标准的患者作为阿司匹林抵抗组(AR组),共166例;阿司匹林敏感的患者200例作为对照组。应用花生四烯酸(AA)作诱导剂测定服药后的血小板聚集功能。并采用聚合酶链反应-限制性核酸内切法(PCR-RFLP)检测COX1、COX2、TBXA2R的基因多态性。结果:阿司匹林抵抗的发生率约为5.76%(166/2 881)。三个基因共8个tag SNPs位点[COX1(rs3842788、rs4273915、rs7866582);、COX2(rs3218625);TBXA2R(rs2238630、rs2238631、rs2238633、rs3786989)]野生型、杂合子及纯合子的基因型频率在两组之间差异无统计学意义。结论:规律服药的冠心病患者阿司匹林抵抗的发生率并不高。COX1、COX2以及TBXA2R基因单核苷酸多态性与阿司匹林抵抗的发生无明显关系。Objective： To explore aspirin resistance（AR） phenomenon in patients with coronary artery disease（CAD） for secondary prevention and to study the relationships between AR and COX1, COX2, TBXA2 R gene polymorphisms.Methods： A total of 2881 CAD patients taken aspirin（100 mg/day） in 7 consecutive days were enrolled. Among them, 2 groups were established as AR group, n=166 and Control group, n=200 aspirin sensitive patients. Platelet aggregation function was induced by arachidonic acid（AA）, COX1, COX2 and TBXA2 R gene polymorphisms were examined by polymerase chain reaction-restricted fragment length polymorphisms（PCR-RFLP） method.Results： The occurrence rate of AR was 5.76%（166/2881）. There were 8 tag SNPs locus in 3 genes as in COX1：（rs3842788）,（rs4273915）,（rs7866582）; in： COX2（rs3218625）; in TBXA2R：（rs2238630）,（rs2238631）,（rs2238633）,（rs3786989）. The frequencies of wild type, heterozygous genotype and homozygous genotype were similar between 2 groups.Conclusion： The incidence rate of AR is not high in CHD patients with regular aspirin medication; single nucleotide gene polymorphisms of COX1, COX2 and TBXA2 R have no obvious correlation to AR.

关 键 词：阿司匹林抵抗 多态性 单核苷酸 基因 

分 类 号：R54[医药卫生—心血管疾病]