Distribution Characteristics Of CYP2C19 Gene Polymorphism In Parts Of China

Objective:Explore characteristics and significance of the distribution of CYP2C19 gene polymorphism in different regions of China,to provide data for individualized clinical treatment,disease prevention and health management.Methods:The genotype of CYP2C19 related to clopidogrel metabolic was detected by polymerase chain reaction microarray hybridization in 2748 Han patients with coronary heart disease(CHD)admitted to the Northern Theater Command general hospital from January 2016 to January 2018.These patients were grouped according to gender and age.Chi-square test was adopted to analysis the prevalence of CYP2C19 genotypes and*2,*3 allele in CHD patients with different age and sex.At the same time,according to CYP2C19 allele grouping,Kruskal-Wallis test was used to further explore the relationship between CYP2C19 allele and the age of CHD patients.Then Pubmed,Embase,Cochrane Library,Web of Science,CNKI,Wan Fang and VIP databases were used to collect documents related to the distribution of CYP2C19 gene polymorphism in Chinese patients with CHD and before April 2018 and in Chinese healthy Han population before August 2018.According to inclusion and exclusion criteria,articles included.The data were collected and the prevalence of CYP2C19*1/*1,*1/*2,*1/3,*2/2,*2/*3,*3/*3 genotypes and CYP2C19*2,*3 alleles were pooled by Stats Direct 3.0.113.0 software using random effect model.Q test and I2 statistics were used to test the heterogeneity,Egger test was used to test the publication bias.Results:1.The frequencies of CYP2C19*1/*1,CYP2C19*1/*2,CYP2C19*1/*3,CYP2C19*2/*2,CYP2C19*3/*3,CYP2C19*2/*3 in Han patients with CHD in Shenyang,china were 41.7%,39.3%,5.8%,9.8%,0.4%,3.0%respectively,the frequencies of CYP2C19*2 and CYP2C19*3 alleles were 30.7%and 4.8%respectively,extensive metabolizers(EM),intermediate metabolizers(IM),poor metabolizers(PM)were 41.7%,45.1%,13.2%respectively.2.There was no statistically significant in the distribution of CYP2C19 genotypes,CYP2C19*2,*3 alleles and clopidogrel metabolic type among patients of different gender with CHD(x2=0.032-9.205,P>0.05).There was statistically significant in the distribution of CYP2C19*2,*3 allele and CYP2C19 genotypes in patients of different ages with CHD according to age groups(<45;45-59;60-75;>75)(x2=17.718-48.772,P<0.001).There was no statistically significant in the distribution of clopidogrel metabolic type in patients with CHD at different ages(x2=4.442,P=0.61 7).According to CYP2C19 allele grouping(CYP2C19*1 group,*2 group,*3 group,carrying both*2 and*3 alleles),Kruskal-Wallis test showed that there were statistically differences in age levels between CYP2C19*1 group and CYP2C19*2/*3 group(adjusted P=0.02),CYP2C19*2 group and CYP2C19*2/*3 group(adjusted P=0.001),but there were differences in age levels between CYP2C19*2 group and CYP2C19*2/*3 group(adjusted P=0.001).There was no statistically difference in age level among patients with CYP2C19*1(adjusted P=0.096),which could not explain the relationship between age and the incidence of CYP2C19*2 in patients with CHD.3.A total of 38 articles were included,including 16981 patients with CHD from 15 provinces,2 municipalities and 3 nations.The pooled proportion of CYP2C19*1/*1,*1/*2,*1/*3,*2/*2,*2/*3,*3/*3、CYP2C19*2,*3 alleles were 42.48%,38.86%,6.49%,8.55%,2.93%,0.40%,29.743%,5.06%。There was significant heterogeneity in the incidence of CYP2C19 genotype and allele in all patients with CHD.Subgroup analysis showed that the heterogeneity was significantly reduced.The distribution of CYP2C19 gene polymorphism in patients with CHD in different regions and nationalities was significantly different.4.A total of 14 articles were included,including 2818 healthy participants.Heterogeneity test showed that there was significant heterogeneity among the studies(P=0.025-0.098).One study was excluded by sensitivity analysis.Heterogeneity decreased significantly.The combined incidence of random effect model was used.The results of Egger test showed that there was no publication bias(P>0.1).The incidence of CYP2C19*1/*1,CYP2C19*1/*2,CYP2C19*1/*3,CYP2C19*2/*2,CYP2C19*3/*3 and CYP2C19*2/*3 genotypes in Chinese Han healthy population were 41.9%,36.9%,7.5%,9.6%,0.5%and 4.6%,respectively.The incidence of CYP2C19*1,*2 and*3 alleles were 63.8%,30.1%and 6.2%respectively.Conclusion:1.The distribution of CYP2C19*2,*3 alleles,genotypes of CYP2C19 in CHD patients of Han nationality in Shenyang area was related with age,and not related with gender.It is not clear whether the incidence of CYP2C19*2 allele is related to age in patients with CHD according to reverse validation.2.There were statistically regional and ethnic differences of CYP2C19 genetic polymorphisms among Chinese patients with CHD.3.There were no obvious regional and ethnic differences of CYP2C19 genetic polymorphisms among healthy Chinese Han population.4.The incidence of CYP2C19*2 allele was 30.1%and 31.9%in healthy Han population and CHD population.That’s almost twice as much as the Caucasians.CYP2C19*2 allele may not be a risk factor for CHD,but further clinical studies are needed to prove it.