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目的:探讨细胞色素P450 3A5基因(CYP3A5)单核苷酸多态位点rs3800959与氯吡格雷抵抗(Clopidogrel resistance,CR)发生的关系。方法:于2010年3月至2011年10月期间,连续入选在沈阳军区总医院心内科住院的接受标准双联抗血小板治疗(阿司匹林+氯吡格雷)的冠心病患者共800例。以光学比浊法测定20μmol/L浓度ADP诱导的残余血小板聚集率(Residual plateletagglutination,RPA),并定义RPA≥70%为CR,所有入选患者分为CR组和氯吡格雷非抵抗组(Non-clopidogrel resistance,NCR)。所有入选病例提取血液白细胞基因组DNA后,采用直接测序的方法测定CYP3A5基因rs3800959单核苷酸多态位点的基因型及等位基因。结果:所入选的800例病人中,CR组为150例,NCR组为650例,CR发生率为18.75%。rs3800959基因型频率在CR组为TT型110例(73.3%)、CT型39例(26.0%)及CC型1例(0.7%);NCR组rs3800959基因型频率分别为477例、159例及14例(73.4%、24.5%及2.1%)。两组间各基因型频率分布无统计学差异(P=0.460,x2=1.554);T、C等位基因分布频率在两组间亦无明显差异(P=0.784,OR=0.942,95%CI=0.655~1.356)。结论:CYP3A5基因单核苷酸多态位点rs3800959与冠心病人CR的发生无相关关系。
Objective: To investigate the relationship between CYP3A5 single nucleotide polymorphism rs3800959 and Clopidogrel resistance (CR). Methods: From March 2010 to October 2011, a total of 800 CHD patients admitted to Department of Cardiology, Shenyang Military Region General Hospital received standard dual antiplatelet therapy (aspirin plus clopidogrel). Residual platelet aggregation (RPA) induced by 20 μmol / L ADP was determined by optical turbidimetry. CR was defined as RPA≥70%. All patients were divided into CR group and non-clopidogrel non-resistant group clopidogrel resistance, NCR). All the selected cases of blood leukocyte DNA extraction, direct sequencing method for CYP3A5 rs3800959 single nucleotide polymorphism locus genotypes and alleles. RESULTS: Of the 800 patients enrolled, 150 were in the CR group, 650 in the NCR group and 18.75% in the CR group. The frequency of rs3800959 genotype in CR group was 110 (73.3%) for TT, 39 (26.0%) for CT and 1 (0.7%) for CC. The frequencies of rs3800959 in NCR group were 477, 159 and 14 Cases (73.4%, 24.5% and 2.1%). There was no significant difference in genotype distribution between the two groups (P = 0.460, x2 = 1.554). There was no significant difference between the two groups in the frequencies of T and C alleles (P = 0.784, OR = 0.942, 95% CI = 0.655 ~ 1.356). Conclusion: There is no correlation between rs3800959, a single nucleotide polymorphism of CYP3A5 gene and CR in CHD patients.