The Relationship Between CYP2C19 Polymorphisms And Clopidogrel Anti-Platelet Reactivity In Elderly Patients

Objective This research analysed the cytochrome p450 2C19(CYP2C19) *2(681G>A),*3(636G>A) polymorphisms of elderly patients who accepted antiplatelet therapy of clopidogrel(over 6 months). To compared the differences of maximum platelet aggregation rate(MPA) and high on-treatment platelet reactivity(HPR) among CYP2C19 extensive metabolizers(EMs), intermediate metabolizers(IMs) and poor metabolizers(PMs) and to analysis the effect of CYP2C19 polymorphism played on the patients who accepted clopidogrel antiplatelet therapy.Methods One hundred thirty three cases of old patients who accepted clopidogrel treatment over 6 months were enrolled. MPA tests assessed by light transmittance aggregometry(LTA). The polymorphism of CYP2C19 were assessed by gene chips. EMs(CYP2C19*1/*1), IMs(CYP2C19*1/*2,*1/*3) and PMs(CYP2C19 *2/*2 *2/*3,*3/*3) were defined by the genotype of CYP2C19. Basic clinical data, clinical history, treatment information,laboratory tests, HPR and MPA were assessed and compared.The results were analyzed by SPSS17.0.Results(1) The observed genotype distributions for the CYP2C19*1,*2,*3 polymorphisms in patients were in accordance with Hardy-Weinberg equilibrium.(2) The phenotype of CYP2C19 included 44(33.1%) EMs(CYP2C19*1/*1), 69(51.9%) IMs(CYP2C19*1/*2, CYP2C19*1/*3) and 20(15.0%) PMs(CYP2C19*2/*2, CYP2C19*2/*3, CYP2C19*3/*3). The proportion of heterozygous and homozygous mutant type was 66.9%.(3) There were no statistical differences of basical data, treatment information and laboratory tests between EMs, IMs and PMs groups(P>0.05).(4) Patients with homozygous mutant type had significantly higher maximum platelet aggregation rate than those with wild type and heterozygous mutant type. Mean MPA were EMs 32.62±15.54%, IMs 36.83 ± 14.34%, PMs 44.70±11.9%, respectively.(5) The rate of MPA≧46%(HPR) was 19.5%(n=26).The rate of HPR in EMs, IMs and PMs were 15.9%(n=7), 18.8%(n=13) and 30.0%(n=6), respectively.(6)The CYP2C19*2 carriers showed an obviously higher platelet aggregation rate compared with the non-carriers [(38.76±13.78%) vs(32.62±15.54%), P=0.045)]. Univariate analysis showed that only CYP2C19*2 variant was significantly related with ADP-induced platelet aggregation rate after clopidogrel treatment(P=0.011). After adjusting the impact of age, gender, body mass index, comorbidities, concomitant medications and so on, stepwise multiple regression showed that CYP2C19*2 was still significantly related with ADP-induced platelet aggregation rate after stable clopidogrel treatment.Conclusion 1. The loss of function variant rate of CYP2C19 in this study is 66.9%. 2. The CYP2C19 polymorphism influences the platelet-inhibition-effect of clopidogrel. Compared to CYP2C19 wild type and heterozygous mutation carriers, the one who carries CYP2C19 homozygous mutation shows a higher platelet aggression rate. 3. CYP2C19*2 is the major pharmacogenomics determinant which affects clopidogrel antiplatelet reactivity in elderly patients with.