PON1基因启动子多态性及非遗传因素对PCI术后抗血小板治疗临床效应的影响

Impact of the polymorphisms within PON1 gene promoter and nongenetic factors on the clinical efficacy of the antiplatelet treatment in patients undergoing percutaneous coronary intervention

目的对氧磷脂酶1(PON1)启动子CpG岛区基因多态性可能会影响氯吡格雷的抗血小板疗效。本研究探讨PON1基因启动子区多态性位点-108C/T,-126 G/C和-162G/A以及高血压、糖尿病等非遗传因素对行经皮冠状动脉介入治疗(PCI术)的冠心病患者氯吡格雷抗血小板临床效应的影响。方法根据纳入和排除标准,入选在广东省人民医院行PCI术患者538名,收集患者的临床资料,采用PCR直接测序的方法检测基因型,使用SAS9.1和HPlus软件分析其与氯吡格雷抗血小板效应的关系。结果 PON1启动子区-108C/T,-126 G/C和-162G/A位点,基因型为野生型或突变性对氯吡格雷抗血小板效应差异均无显著性(P>0.05);患者合并高血压[HR(95%CI)=3.837]、糖尿病(HR=2.715)或使用钙离子拮抗剂(HR=2.686)时,PCI术后出现MACE的风险较高(P<0.05)。结论 PON1基因启动子CpG岛区-108C/T,-126 G/C和-162G/A基因变异对接受氯吡格雷抗血小板治疗的冠心病患者在PCI术后出现主要不良心脏事件(MACE)无明显影响。患者合并高血压、糖尿病或使用钙离子拮抗剂会增加PCI术后出现MACE的风险。

Aim The antiplatelet efficacy of clopi-dogrel may be affected by gene polymorphisms within CpG island in the PON1 promoter region.The present study was aimed to determine the association of genetic variants（-108C / T,-126 G / C and-162G / A within the PON1 promoter region） and nongenetic factors（hypertension and diabetes mellitus etc） with the antiplatelet efficacy of clopidogrel in Han Chinese patients after percutaneous coronary intervention（PCI）.Methods Five hundred and thirty eight patients undergoing PCI and received dual-antiplatelet therapy were sequentially recruited in Guangdong General Hospital according to the inclusion and exclusion criteria.Clinical data of the patients were collected,genotyping of the polymorphisms studied were determined by the PCR-direct sequencing method,and data analyses were performed using SAS9.1 and HPlus software.Results None of the genetic variants（-108C / T,-126 G / C and-162G / A） was associated with the anti-platelet efficacy of clopidogrel（P 0.05）.Coronary heart disease patients complicated with hypertension（HR = 3.837）,diabetes mellitus（HR = 2.715） or use of calcium antagonist（HR = 2.686） had a higher risk of MACE.Conclusions Genetic variants within PON1 promoter do not have a significant impact on the antiplatelet efficacy of clopidogrel in patients undergoing PCI.However,hypertension,diabetes mellitus or use of calcium antagonist increase the risk of MACE.