本研究回顾性分析了年龄和性别对PON1 Q192R基因多态性与氯吡格雷抗血小板疗效之间相关性的影响.收集1254例纳入研究的患者连续服用标准双抗≥3天后测得的血小板聚集率(PAR),将PAR>50%定义为氯吡格雷抵抗(CR).比较不同年龄组及不同性别的人群中PON1 Q192R基因型与CR的相关性.本研究人群PON1 Q192R最小等位基因频率(minor allele frequency,MAF)为37%.在整体人群中,PON1 Q192R突变纯合型(A/A)患者中CR发生率(59.39%)与野生型(G/G)患者(43.58%)及突变杂合型(G/A)患者(49.00%)中CR发生率相比具有显著差异(P265岁的老年患者中,不同基因型CR发生率虽有不同,但差异无统计学意义(P1,P2,P3>0.05).男性患者中CR发生率45.87%)显著低于女性(53.91%,P=0.01).同时,在男性患者中,G/G型患者CR的发生率(40.63%)与A/A型(57.02%)相比有显著性差异(P20.05).高龄和女性作为CR的独立危险因素,会削弱PON1 Q192R基因多态性造成的个体间氯吡格雷抗血小板疗效的差异.%Objective: To investigate the association between the gene polymorphism of PON1 Q192R and the occurrence of clopidogrel resistance (CR) among different age groups and gender groups. Methods: A total of 1254 patients were enrolled. Detailed clinical information and genetypes of PON1 Q192R of each patient was collected. Platelet reactivity was measured with platelet aggregation rate (PAR) which was detected when continuously taking standard antiplatelet drugs more than 3 days. PAR >50% was defined as CR. The patients were divided into different grous based on their age and gender. Then the correlation of CR and PON1 Q192R in different groups was analyzed. Results: The minor allele frequency (MAF) in our study population was 37%. In PON1 Q192R mutant homozygous type (A/A) group, the rate of CR was 59.39%, which was significantly higher than that of wild-type (G/G) group (43.58%) and mutant heterozygous type (G/A) group (49.00%) (P2 0.05). The rate of CR in male patients (45.87%) was significantly lower than that in female patients (53.91%, P2 = 0.01). Moreover, in male patients, the rate of CR in G/G group (40.63%) was significantly different from that in A/A group (57.02%, P2 0.05). Conclusion: Advanced age and femininity might be the independent risk factors of CR, which could weaken the influence of PON1 Q192R on individual differences of clopidogrel treatment. The correlation of PON1 Q192R and CR was much more significant in male patients younger than 65 years old.
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