CYP2 C19基因多态性与急性脑梗死患者氯吡格雷疗效的相关性研究

摘要

目的：探讨急性脑梗死患者CYP2C19基因多态性与氯吡格雷疗效的相关性。方法采用限制性片段长度多态性PCR法对171例急性脑梗死患者进行CYP2C19基因多态性检测。所有患者给予氯吡格雷治疗2周。分别于治疗前及治疗后第1d、第5d进行血小板聚集率检测，于治疗前及治疗后第1周、第2周进行NIHSS和日常生活活动能力评价（ ADL）评分。计算血小板聚集抑制率并进行分析。结果本组171例患者中野生型纯合子（A组）79例，均为CYP2C19*1／*1；野生型基因与突变基因杂合子（B组）71例，包括55例CYP2C19*1／*2及16例 CYP2C19*1／*3；突变基因纯合子或杂合子（ C 组）21例，包括11例CYP2C19*2／*2、9例CYP2C19*3／*3及1例CYP2C19*2／*3。治疗后第1 d及第5 d时，3组间血小板聚集抑制率的比较差异均有统计学意义（均P＜0．05）。与治疗前比较，3组治疗后第1周、第2周NIHSS评分均显著降低，ADL评分均显著升高（均P＜0．05）。与A组比较，B组及C组治疗后第1周、第2周NIHSS评分均明显升高，ADL评分均明显降低（均P＜0．05）。多因素Logistic回归分析显示，吸烟（ OR＝1．584，95％CI：1．079～2．136，P＝0．004）及CYP2C19基因多态性（OR＝1．837，95％CI：1．106～2．540，P＝0．002）均与急性脑梗死患者血小板聚集抑制率独立相关。结论 CYP2C19基因多态性可影响急性脑梗死患者氯吡格雷治疗的疗效。%Objective To observe the correlation between the gene ploymorphisms of CYP2C19 and the curative effects of clopidogrel in patients with acute cerebral infarction.Methods The gene polymorphisms of CYP2C19 were tested in 171 acute cerebral infarction patients by PCR-restriction fragment length polymorphism method. All participants were treated with clopidogrel for 2 weeks.The platelet aggregation rates before treatment and 1 d, 5 d after treatment were detected.NIHSS and activities of daily living ( ADL) were detected before treatment and 1 week, 2 weeks after treatment.The inhibition rate of platelet aggregation ( IPA) was calculated and analyzed.Results In the 171 patients, homozygous wild CYP2C19 genotype was found in 79 cases (A group), with CYP2C19 *1/*1;heterozygous wild and mutant CYP2C19 genotype was found in 71 cases ( B group ) , including 55 cases with CYP2C19 *1/*2 and 16 cases with CYP2C19 *1/*3; homozygous or heterozygous mutant CYP2C19 genotype was found in 21 cases (C group), including 11 cases with CYP2C19*2/*2, 9 cases with CYP2C19*3/*3 and 1 cases with CYP2C19 *2/*3.The differences of IPA among the 3 groups were statistically significant at 1 d, 5 d after treatment (all P<0.05).Compared with before treatment, the NIHSS scores of the 3 groups at 1 week, 2 weeks after treatment were significantly decreased, and the ADL scores were significantly increased ( all P<0.05 ) . Compared with the A group, the NIHSS scores of B group and C group at 1 week, 2 weeks after treatment were significantly increased, and the ADL scores were significantly decreased (all P<0.05).Multiple Logistic regression analysis showed that smoking (OR=1.584,95%CI:1.079-2.136,P=0.004) and CYP2C19 gene polymorphisms (OR=1.837,95%CI:1.106 -2.540,P=0.002) were independently correlated with IPA in patients with acute cerebral infarction.Conclusion CYP2C19 gene ploymorphisms have influence on the curative effects of clopidogrel in patients with acute cerebral infarction.