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目的观察汉族人群冠心病患者的细胞色素P450 2C19(CYP2C19)基因多态性以及与氯吡格雷反应性的相关性。方法用DNA微阵列芯片法检测626例冠心病患者的CYP2C19基因型,依据第636号及第681号碱基对等位基因功能缺失的不同,分为快代谢型(EM:*1/*1)、中间代谢型(IM:*1/*2、*1/*3)和慢代谢型(PM:*2/*2、*2/*3、*3/*3)3组;用光密度比浊法检测患者入院时及服用氯吡格雷24 h后的最大血小板聚集率(MAP)。结果在626例检测标本中,EM基因型292例,发生率为46.65%;IM基因型为244例,发生率为38.98%;PM基因型90例,发生率为14.38%。服用氯吡格雷24 h后,EM基因型的MAP为(21.29±4.42)%,明显低于IM基因型的(27.54±5.38)%及PM基因型的(32.69±6.18)%,差异均有统计学意义(P<0.05)。有142例(22.68%)患者出现氯吡格雷抵抗,包括17例EM基因型、86例IM基因型、39例PM基因型,EM基因型出现氯吡格雷抵抗的几率为5.83%,明显低于IM基因型的35.25%及PM基因型的43.33%,各代谢型组间比较差异有统计学意义(P<0.05)。结论湖北黄石地区汉族人群冠心病患者CYP2C19基因多态性与氯吡格雷反应性呈相关性,IM基因型及PM基因型患者使用氯吡格雷治疗的效果较差,风险较高。
Objective To investigate the genetic polymorphism of cytochrome P450 2C19 (CYP2C19) and its relationship with clopidogrel reactivity in Chinese Han population with coronary heart disease. Methods CYP2C19 genotypes were detected by DNA microarray in 626 patients with coronary heart disease. According to the loss of allelic function of base pairs 636 and 681, the CYP2C19 genotypes were divided into two groups: fast metabolizing (EM: * 1 / * 1 ), Intermediate metabolic group (IM: * 1 / * 2, * 1 / * 3) and slow metabolism group (PM: * 2 / * 2, * 2 / * 3, * 3 / * 3) Nephelometry was used to determine the maximum platelet aggregation rate (MAP) at admission and after clopidogrel exposure for 24 h. Results In 626 samples, the genotype of EM was 292 cases, the incidence was 46.65%. The IM genotype was 244 cases, the incidence was 38.98%. The PM genotype was 90 cases, the incidence was 14.38%. After taking clopidogrel for 24 h, MAP of EM genotype was (21.29 ± 4.42)%, which was significantly lower than that of IM genotype (27.54 ± 5.38)% and PM genotype (32.69 ± 6.18)% Significance (P <0.05). There were 142 patients (22.68%) with clopidogrel resistance, including 17 EM genotypes, 86 IM genotypes and 39 PM genotypes. The odds of clopidogrel resistance in EM genotype was 5.83%, which was significantly lower than 35.25% of IM genotypes and 43.33% of PM genotypes. There was significant difference among all metabolic groups (P <0.05). Conclusion CYP2C19 polymorphism in CHD patients with CHD in Huangshi district of Hubei Province is associated with the response to clopidogrel. The patients with IM genotype and PM genotype are less effective and have a higher risk of using clopidogrel.