- 期刊
Systematic data on the Genetic Polymorphisms of CYP2C19 in the Chinese Han Population
並列摘要
The genetic polymorphisms of cytochrome P450 enzymes 2C19 (CYP2C19) result in substantial inter-individual and interethnic variability in drug excretion rates and steady-state serum concentrations. To date, very few pharmacogenetic data are available on the genetic polymorphisms of CYP2C19 in the Chinese Han population. In this study, we investigate the 5'-regulatory region, all the exons and their surrounding introns of CYP2C19 gene in 400 unrelated healthy Chinese Han volunteers from four different geographical locations namely Shanghai, Shantou, Shenyang and Xi'an with a sample of 100 subjects in each population. Fourteen different CYP2C19 polymorphisms, including one novel variant (-2306G＞A) in the enhancer region and a novel non-synonymous one (905C＞G, T302R), were identified. Some of these polymorphisms demonstrate significant differences among populations from the four different cities, such as -889T＞G, IVS3-23T＞C, and 991C＞T. In addition, CYP2C19*1,*2,*3,*15,*17 alleles showed frequencies 69.7%, 24.7%, 3.3%, 1.2%, 1.2%, respectively, and fifteen genotypes were determined in the present study. CYP2C19*15 was the first such findings in an Asian population. The frequencies of the prevalent defective alleles CYP2C19*2 and CYP2C19*3 in Chinese Han populations are similar to those in other Asians and much higher than those reported in American European and other Caucasian populations. Haplotype analysis demonstrated different frequencies among the four geographical populations. Our study established the profile of CYP2C19 polymorphisms in the Chinese Han population and could be helpful for future personalized medicine studies in Asian populations generally.