年龄与性别对氯吡格雷抗血小板疗效与PON1 Q192R基因多态性相关性的影响  

The influence of age and gender on the association between the genetic polymorphism of PON1 Q192R and the effect of clopidogrel

作　　者：徐晓宇[1] 石秀锦[1] 续茜桥 彭文星[1] 林阳[1] 

机构地区：[1]首都医科大学附属北京安贞医院药剂科,北京100029

出　　处：《中国药物应用与监测》2017年第3期146-150,共5页Chinese Journal of Drug Application and Monitoring

基　　金："重大新药创制"科技重大专项课题(2012ZX09303016)

摘　　要：目的: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。方法: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。结果: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(P2<0.001,P3=0.02)。在≤65岁的患者中,G/G型患者的CR发生率(41.69%)与A/A型(57.58%)相比有显著性差异(P2<0.001),而在>65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(P2<0.001),而在女性患者中,不同基因型的患者间,CR发生率无明显差异(P1,P2,P3>0.05)。结论: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 defned 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 signifcantly higher than that of wild-type （G/G） group （43.58%） and mutant heterozygous type （G/A） group （49.00%） （P2 〈 0.01, P3 = 0.02 〈 0.05）. In patients younger than or equal to 65 years old, the rate of CR in G/G group （41.69%） was signifcantly different from that in A/A group （57.58%） （P2 = 0.00）, while there was no signifcant difference in the rate of CR among patients older than 65 years old （P1, P2, P3 〉 0.05）. The rate of CR in male patients （45.87%） was signifcantly 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 signifcantly different from that in A/A group （57.02%, P2 〈 0.001）, while there was no signifcant difference in the rate of CR among female patients with different PON1 Q192R mutant type （P1, P2, P3 〉 0.05）. Conclusion： Advanced age and femininity might be the independent risk factors of CR, which could weaken the infuence of PON1 Q192R on individual differences of clopidogrel treatment. The correlation of PON1 Q192R and CR was much more signifcant in male patients younger than 65 years old.

关 键 词：氯吡格雷 PON1 Q192R 年龄 性别 

分 类 号：R97[医药卫生—药品]