GPⅠa基因C807T及P2Y1基因A1622G二态性与阿司匹林抵抗的相关性研究

Correlation between aspirin resistance and GPⅠa gene C807T and P2Y1 gene A1622G dimorphism

目的：研究血小板膜糖蛋白（GP）Ⅰa基因C870T及二磷酸腺苷受体P2Y1基因A1622G多态性与阿司匹林抵抗的相关性。方法选取2012年3～12月在本院急诊内科病房住院患者中入选服用阿司匹林的心血管疾病患者（包括冠心病、高血压、脑梗死后）190例，通过测定血小板聚集率将病例分为阿司匹林抵抗（AR）组和阿司匹林敏感（AS）组，对GPⅠa基因C807T及P2Y1基因A1622G的基因位点进行直接测序法检测，然后进行基因频率的对比，并通过Logistic回归模型分析T807、G1622与AR的关联性。结果55例（29％）患者存在AR，其GPⅠa基因C807T的T等位基因频率及TC＋TT基因型的频率（χ2＝12.848，P＜0.05及χ2＝6.138，P＜0.05）和P2Y1基因 A1622G 的 G等位基因频率及 AG ＋GG基因型的频率（χ2＝8.527，P＜0.05及χ2＝5.346，P＜0.05）均显著高于AS组。 Logistic回归分析GPⅠa T807和P2Y1G1622等位基因与阿司匹林抵抗的发生显著相关（OR＝4.36，95％可信区间为2.86～9.38，P＜0.05；OR＝3.76，95％可信区间为2.87～10.52，P＜0.05）。结论 GPⅠa基因807C＞T以及P2Y1基因1622A＞G变异与阿司匹林抵抗发生率增加有关。

Objective To investigate correlation between aspirin resistance （ AR） and platelet membrane glycoprotein（GP）Ⅰa gene C807T and P2Y1 gene A1622G polymorphisms.Methods We enrolled 190 cases who were taking aspirin with coronary heart disease ,hypertension and cerebral infarction in our emergency medical ward from March 2012 to December 2012.By measuring the platelet aggregation rate ,they would be divided into cases of AR and aspirin sensitive（AS）group.GPⅠa gene C807T and P2Y1 A1622G were directly sequenced,then the gene frequency were compared ,and the relevance between T 807 ,G1622 and AR were analyzed by the Logistic regression model.Results There were 55 cases（29%） patients in AR group,GP Ⅰa gene C807T T and TC ＋TT allele frequency（χ2 =12.848,P 〈0.05 and χ2 =6.138,P 〈0.05） and P2Y1 gene A1622G G and AG ＋GG allele frequency （χ2 =8.527 ,P〈0.05 and χ2 =5.346 ,P〈0.05 ） were significantly higher than the AS group .By Logistic regression model ,GPⅠa T807 and P2Y1G1622 allele were significantly associated with the incidence of AR （ OR=4.36,95% CI 2.86-9.38,P 〈0.05;OR =3.76,95% CI 2.87-10.52,P 〈0.05）.Conclusion There are correlation between mutation of membrane glycoprotein （GP）Ⅰa gene C807T and P2Y1 gene A1622G and increases of occurrence of AR .