Genetic Polymorphism Analysis Of CYP2C19and The Efficacy Of Clopidogrel In Yunnan Han Population

Objective:To investigate the distribution of CYP2C19polymorphisms in Yunnan Han population and evaluate the influence of CYP2C19polymorphisms and the effect of clopidogrel on CHD secondary prevention, for the individualized treatment of clopidogrel.Methods:96cases of patients with healthy check-up were chosed randomly at the Fist Affiliated Hospital of Kunming University from October2011to December2012, the frequency of CYP2C19polymorphisms in96unrelated Yunnan Han population were genotyped by DNA microarray technology, analyze the allele and genotype frequencies of CYP2C19, and a comparison with other populations, realize the feature of CYP2C19polymorphisms in Yunnan Han population. To be divided the population into three classes (extensive metabolisers, intermediate metabolizers, and poor metabolizers) by the basis of metabolic phenotype definition and the result of genotype. From a random sample in the three classes divided into groups of EM (n=12), IM (n=12) and PM (n=12). All Patients received a300mg dose of clopidogrel. The PAC-1and CD62P were assessed by whole-lood flow cytometry at baseline and at4hours and24hours.Results:The distribution of CYP2C19:The frequencies of CYP2C19*1,*2and*3were63.6%,30.7%and5.7%respectively. The genotype frequencies of CYP2C19*1/*1, CYP2C19*1/*2, CYP2C19*1/*3, CYP2C19*2/*2, CYP2C19*2/*3and CYP2C19*3/*3were41.7%,37.5%,6.3%,10.4%,3.1%and1.0%. The data were similar to the report of Jiangsu, Liaoning, Guangdong, Beijing, Gansu, Xingjiang, Zhejiang, Henan of han population in china, and Chinese She, Mongolian, Tibetan, and Japan, Korea, Malaysia, Thailand (P>0.05) but were different from that of Chinese Uygur, Sala, Hui, KazaKh and Iran, Greece, Russia, Egypt, Guinean (P<0.05). The influence of Genetic polymorphism to platelet CD62P, PAC-1expression:The baseline data of CD62P, PAC-1in the three groups (EM, IM, PM) were not significantly different statistically among the three groups (P>0.05); We detected that the levels of platelet activation were falled after taking the medicine4hours later, platelet expression of CD62P and PAC-1were deereased at4,24hours than at baseline (P<0.01); The expression of platelet activation were differentially expressed in the thee groups at24hours low in EM, high in PM, and IM between the two groups, there were significantly different statistically between EM and IM (P<0.01). It found that the maximum reduction of platelet activation were EM, IM second, miximum reduction were PM, there were significantly different statistically between EM and IM (P<0.05).Conclusion:The frequencies of CYP2C19*1,*2and*3in Yunnan han population of China were63.6%.30.7%and5.7%respectively.The genotype frequencies of CYP2C19*1/*1, CYP2C19*1/*2, CYP2C19*1/*3, CYP2C19*2/*2, CYP2C19*2/*3and CYP2C19*3/*3were41.7%,37.5%,6.3%,10.4%,3.1%and1.0%. The data were similar to the report of Jiangsu, Liaoning, Guangdong, Beijing, Gansu, Xingjiang, Zhejiang, Henan of han population in china, and Chinese she, Mongolian, Tibetan, and Japan, Korea, Malaysia,Thailand but were different from that of Chinese Uygur, Sala, Hui, KazaKh and Iran, Greece. Russia, Egypt, Guinean. The PAC-1and CD62P of platelet can be inhibited by clopidogrel. The inhibition of CYP2C19poor metabolizers after oral clopidogrel were weaker than extensive metabolisers.