目的探讨对氧磷酶1(PON1)基因rs854572单核苷酸多态性与氯吡格雷抵抗(CR)发生的相关性。方法采用病例-对照研究的方法,共入选850例沈阳军区总医院冠心病住院患者,采用光学比浊法测定20μmol/L二磷酸腺苷(ADP)诱导的残余血小板聚集率(RPA),当RPA≥70%时,即定义为CR。将入选患者分为CR组(n=215)和非氯吡格雷抵抗(NCR)组(n=635),采用焦磷酸测序法测定PON1基因rs854572单核苷酸多态性的基因型及等位基因分布频率。结果 PON1基因rs854572多态位点在两组间基因型分布频率皆符合Hardy-Weinberg平衡定律,三种基因型(CC、CG和GG)分布频率在CR组和NCR组分别为23.7%、49.3%、27.0%和24.1%、50.2%、25.7%,三种基因型在两组间分布频率差异无统计学意义(P=0.93)。C、G等位基因分布频率在两组间差异亦无统计学意义(P=0.763)。Logistic回归校正性别、年龄、体重指数、吸烟、高血压、高脂血症及糖尿病等冠心病易患因素后,PON1基因rs854572单核苷酸多态性仍与冠心病患者CR的发生无相关关系。结论 PON1基因单核苷酸多态位点rs854572与冠心病患者CR的发生无关。
Objective To investigate the correlation of the single nucleotidepolymorphism (SNP) of PON1 (Paraoxonase-1) gene rs854572 to the occurrence of clopidogrel resistance (CR). Methods A case-control method was employed in present study. A total of 850 hospitalized patients with coronary artery diseases (CAD) in General Hospital of Shenyang Command were enrolled. The residual platelet aggregation rate (RPA) induced by 20~mol/L of adenosine diphosphate (ADP) was detected by optical nephelometry, and RPA~ 70% was defined as CR. Accordingly, all the enrolled 850 patients were then divided into CR group (n=215) and non-CR (NCR) group (n=635). Polymerase chain reaction (PCR) and pyrophosphate sequencing were executed to determine the genotypes and the allele frequencies of PON1 gene rs854572. Results The genotype frequencies in rs854572 of PONt gene conformed well to the Hardy-Weinberg equilibrium in both CR group and NCR group. Three frequencies of genotype CC, CG and GG were 23.7%, 49.3%, 27.0% in CR group, and 24.1%, 50.2%, 25.7% in NCR groups, respectively. No significant difference in genotype and allele frequency existed between CR group and NCR group (P=0.93 and 0.76, respectively). Logistic regression analysis revealed that no correlation between rs854572 SNP of PON1 gene and the formation of CR in patients with CAD after adjustment of correspondent factors including age, gender, body mess index, smoking, hypertension, diabetes mellitus and hyperlipidemia. Conclusions It is considered that no correlation exists between PON1 gene rs854572 polymorpbism and clopidogrel resistance in patients with coronary heart disease.