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

XU Xiao-yu; SHI Xiu-jin; XU Xi-qiao; PENG Wen-xing; LIN Yang

doi:10.3969/j.issn.1672-8157.2017.03.005

Abstract：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 < 0.01, 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 significantly different from that in A/A group (57.58%) (P2 = 0.00), while there was no significant 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 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 < 0.001), while there was no significant 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 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.