335例心脑血管病患者阿司匹林抵抗与环氧化酶2基因多态性位点的相关性

摘要

目的 探讨心脑血管病患者环氧化酶2(COX-2)基因单核苷酸多态性(SNP)位点-1195 G＞A和-765 G＞C与阿司匹林抵抗(AR)的相关性.方法 纳入中国北方汉族冠心病及缺血性脑卒中患者335例,根据血小板聚集率分为AR组27例、阿司匹林半抵抗(ASR)组68例和阿司匹林敏感(AS)组240例.SNP检测采用实时荧光定量PCR方法,使用SHEsis软件构建单体型.并进行分析.结果 AS组、ASR和AR组-1195 G＞A位点的GG、GA、AA分布频率比较,差异有统计学意义(P=0.003);3组1195G＞A位点隐性模型GA+AA和GG基因型分布频率亦存在统计学差异(P＜0.01),3组等位基因A分布频率比较,差异有统计学意义(P=0.009).3组-765G＞C位点基因型、等位基因型分布频率比较,差异无统计学意义(P=0.822).AS组与ASR组、AS组与AR组单体型G-G和AG分布频率均存在统计学差异(P＜0.05,P＜0.01).相关因素校正后,logistic回归分析显示,COX-2的-1195 G＞A GA+AA基因型仍与AR和ASR的发生显著相关(OR=3.381,95％CI:1.439～7.944).结论 COX-2基因的-1195 G＞A等位基因A可能与AR及ASR的发生具有关联性,可能是AR及ASR发生的一个遗传易感性标记位点.%Objective To study the corrlelation between aspirin resistance (AR) and SNP-1195 G＞A and-765 G＞ C of COX-2 gene in cardio-cerebrovascular disease patients.Methods Three hundred and thirty-five Han patients with coronary heart disease and cardio-cerebrovascular disease from Northern China were divided into AR group (n=27),aspirin semi-resistance (ASR)group (n=68) and aspirin sensitivity (AS) group (n=240) according to their platelet aggregation.Their SNP was detected by RT-PCR.Nomomeric genotypes were constructed using the unPHASE software.Results The distribution frequencies of-1195 G＞A genotypes (GG,GA,AA,GA +AA and GG) of COX-2 and allele A were significantly different in AS,ASR and AR groups (P=0.003,P＜0.01,P=0.009).No significant difference was found in the distribution frequencies of-765 G＞C and allele genotypes among the 3 groups (P=0.822).The distribution frequencies of nomomeric GG and GA genotypes were significantly different among the 3 groups (P＜ 0.05,P＜0.01).Logistic regression analysis showed that the-1195 G＞A GA+AA genotypes of COX-2 were significantly correlated with the AR and ASR genotyoes of COX-2 after adjustment for relative factors (OR=3.381,95％CI:1.439-7.944).Conclusion The-1195 G＞A allele A of COX-2 correlates with the occurrence of AR and ASR possibly due to their genetic susceptibility marker sites.