胰岛素受体底物-1基因rs1078533单核苷酸多态性与2型糖尿病合并冠心病患者氯吡格雷抵抗的相关性研究

Relation between rs1078533 polymorphism of IRS-1 gene and clopidogrel resistance in patients with type 2 diabetes mellitus accompanying coronary artery disease

目的探讨胰岛素受体底物-1(insulin receptor substrate-1,IRS-1)基因rs1078533单核苷酸多态性与2型糖尿病合并冠心病患者氯吡格雷抵抗(clopidogrel resistance,CR)发生的相关性。方法入选2012年4月-2013年4月沈阳军区总医院2型糖尿病合并冠心病住院患者325例,采用光学比浊法测定20μmol/L二磷酸腺苷(adenosine diphosphate,ADP)诱导的残余血小板聚集率(residual platelet agglutination,RPA),当RPA≥70%时定义为CR。所有入选患者根据RPA分为CR组(n=142)和非氯吡格雷抵抗(NCR)组(n=183)。采用聚合酶链式反应结合直接测序法测定IRS-1基因rs1078533位点在CR组和NCR组的基因型及等位基因分布频率。结果 IRS-1基因rs1078533多态位点在CR组和NCR组基因型分布频率符合Hardy-Weinberg平衡。三种基因型(AA、AC和CC)在两组的分布频率分别为1.4%、16.8%、81.8%和1.6%、19.8%、78.6%。基因型(AA、AC和CC)及等位基因(A和C)分布频率在CR组和NCR组间均无统计学差异(P=0.786,P=0.524)。Logistic回归分析校正性别、年龄、体质量指数、吸烟和高血压等冠心病和糖尿病易患因素后,IRS-1基因rs1078533单核苷酸多态性仍与2型糖尿病合并冠心病患者CR的发生无相关性。结论 IRS-1基因rs1078533单核苷酸多态性与2型糖尿病合并冠心病患者CR的发生无相关性。

Objective To study the relation between rs1078533 polymorphism of IRS-1 gene and clopidogrel resistance （CR） in Chinese patients with type 2 diabetes mellitus （DM） accompanying coronary artery disease （CAD）. Methods Three hundred and twenty-five patients with type 2 DM accompanying CAD admitted to General Hospital of Shenyang Military Area Command from April 2012 to April 2013 were enrolled in this study. Their residual platelet aggregation rate （RPA） induced by 20 μmol/L adenosine diphosphate （ADP） was measured by optical nephelometry. The CR was defined when the RPA was ≥ 70%. The patients were divided into CR group （n=142） and non-CR group （n=183） according to their RPA. The genotypes and allele frequencies at rs 1078533 of IRS-1 gene in two groups were detected by PCR and pyrophosphate sequencing, respectively. Results The genotype frequencies at rs1078533 of IRS-1 gene conformed to the Hardy-Weinberg equilibrium in two groups. The frequency of genotypes （AA, AC and CC） was 1.4%, 16.8%, 81.8%, respectively, in CR group and 1.6%, 19.8%, 78.6%, respectively, in non-CR group. No significant difference was observed in genotypes and allele frequencies between the two groups （P = 0.786 and P = 0.524）. Logistic regression analysis revealed that the rs1078533 polymorphism was not related with the CR after adjustment of risk factors including age, gender, BMI, smoking and hypertension in patients with type 2 DM accompanying CAD. Conclusion The rs1078533 polymorphism of IRS- 1 gene is not related with the CR in patients with type 2 DM accompanying CAD.