冠心病患者细胞色素P450 2C19^(*)2基因多态性和幽门螺杆菌感染对氯吡格雷治疗效果的评估价值

The evaluation value of cytochrome P450 2C19^(*)2 gene polymorphism,Helicobacter pylori infection for clopidogrel effect in patients with coronary heart disease

目的探讨冠心病患者细胞色素P450 2C19^(*)2(CYP2C19^(*)2)基因多态性和幽门螺杆菌(Hp)感染对氯吡格雷治疗效果的评估价值。方法回顾性分析2016年2月至2020年3月苏州高新区人民医院113例冠心病患者的临床资料。采用聚合酶链反应-限制性(内切酶)片段长度多态性(PCR-RFLP)法检测CYP2C19^(*)2基因多态性,采用13C尿素呼气试验检测Hp感染情况。患者均给予氯吡格雷治疗,治疗4周后评估治疗效果。采用受试者工作特征(ROC)曲线分析CYP2C19^(*)2基因多态性和Hp感染对冠心病患者氯吡格雷治疗效果的预测效能。结果冠心病患者CYP2C19^(*)2基因型符合Hardy-Weinberg平衡(χ^(2)=0.33,P>0.05)。113例冠心病患者中,Hp感染27例,Hp未感染86例。Hp感染患者CYP2C19^(*)2基因GG型2例,GA型6例,AA型19例;Hp未感染患者CYP2C19^(*)2基因GG型23例,GA型46例,AA型17例,两者CYP2C19^(*)2基因多态性比较差异有统计学意义(χ^(2)=24.35,P<0.01)。氯吡格雷治疗后有效79例,无效34例。有效患者CYP2C19^(*)2基因GG型20例,GA型43例,AA型16例;无效患者CYP2C19^(*)2基因GG型5例,GA型9例,AA型20例,两者CYP2C19^(*)2基因多态性比较差异有统计学意义(χ^(2)=16.35,P<0.01)。有效患者Hp感染率明显低于无效患者[12.66%(10/79)比50.00%(17/34)],差异有统计学意义(χ^(2)=18.23,P<0.01)。ROC曲线分析结果显示,CYP2C19^(*)2基因多态性联合Hp感染评估冠心病患者氯吡格雷治疗效果的曲线下面积明显大于CYP2C19^(*)2基因GG型、GA型、AA型及Hp感染的单独评估(0.973比0.869、0.679、0.884、0.728)。结论冠心病患者CYP2C19^(*)2基因多态性与Hp感染有关,与Hp感染联合检测对氯吡格雷治疗效果具有评估价值。

Objective To explore the evaluation of cytochrome P450 2C19^(*)2(CYP2C19^(*)2)gene polymorphism and Helicobacter pylori(Hp)infection for clopidogrel efficacy in patients with coronary heart disease.Methods The clinical data of 113 patients with coronary heart disease from February 2016 to March 2020 in Suzhou High-tech Zone People′s Hospital were retrospectively analyzed.The CYP2C19^(*)2 gene polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)method,the Hp infection was detected by 13C urea breath test.The patients were treated with clopidogrel,the effect after 4 weeks was evaluated.The receiver operating characteristic(ROC)curve was used to evaluate the CYP2C19^(*)2 gene polymorphism and Hp infection for evaluating clopidogrel effect in patients with coronary heart disease.Results The CYP2C19^(*)2 genotype in patients with coronary heart disease conformed to Hardy-Weinberg balance(χ^(2)=0.33,P>0.05).Among 113 patients with coronary heart disease,Hp infection was in 27 cases,and Hp non-infection in 86 cases.Among Hp infection patients,CYP2C19^(*)2 gene GG was in 2 cases,GA in 6 cases,AA in 19 cases;among Hp non-infection patients,CYP2C19^(*)2 gene GG was in 23 cases,GA in 46 cases,AA in 17 cases,there was statistical difference in CYP2C19^(*)2 gene polymorphism between the two(χ^(2)=24.35,P<0.01).After clopidogrel treatment,effectiveness was in 79 cases,inefficiency in 34 cases.Among effectiveness patients,YP2C19^(*)2 gene GG was in 20 cases,GA in 43 cases,AA in 16 cases;among inefficiency patients,CYP2C19^(*)2 gene GG was in 5 cases,GA in 9 cases,AA in 20 cases,there was statistical difference in CYP2C19^(*)2 gene polymorphism between the two groups(χ^(2)=16.35,P<0.01).The rate of Hp infection in effectiveness patients was significantly lower than that in inefficiency patients:12.66%(10/79)vs.50.00%(17/34),and there was statistical difference(χ^(2)=18.23,P<0.05).ROC curve analysis result showed that the area under the curve of CYP2C19^(*)2 gene polymorphism combined with Hp infection for evaluating clopidogrel effect in patients with coronary heart disease was larger than CYP2C19^(*)2 gent GG,GA,AA and Hp infection alone evaluating(0.973 vs.0.869,0.679,0.884 and 0.728).Conclusions The CYP2C19^(*)2 gene polymorphism is associated with Hp infection in patients with coronary heart disease,and the CYP2C19^(*)2 gene polymorphism combined with Hp infection has the evaluation value for the efficacy of clopidogrel.