Polymorphisms and phenotypic analysis of cytochrome P450 2D6 in the Tibetan population

Abstract

The cytochrome P450 2D6 enzyme (CYP2D6) metabolizes about 25% of prescribed drugs in the endoplasmic reticulum, and genetic polymorphisms in CYP2D6 can greatly affect its activity and lead to differences among individuals in drug efficacy and adverse drug reactions. To investigate genetic polymorphisms in CYP2D6 among Tibetan Chinese, we directly sequenced the whole gene in 96 unrelated, healthy Tibetans from The Tibet Autonomous Region of China and screened for genetic variants in the promoter, exons, introns, and 3'UTR. We detected fifty-one genetic polymorphisms in CYP2D6, and 16 of them are novel. The allele frequencies of CYP2D6*1, *2, *5, *10, *41, and *49 were 0.25, 0.43, 0.02, 0.29, 0.02, and 0.01, respectively. The frequency of CYP2D6*10, a putative poor-metabolizer allele, was lower in our sample population compared with that in the Han Chinese population (p<0.001). In addition, haplotype analysis allowed 15 CYP2D6 haplotypes to be classified into three groups. In conclusion, our results provide basic information about CPY2D6 alleles in Tibetans and suggest that the enzymatic activities of CYP2D6 may differ among the diverse ethnic populations of China. Our results provide a basis for safer drug administration and better therapeutic treatment among Tibetans.

Keywords: CYP; CYP2D6; DNA; EM; Ethnic difference; Genetic polymorphism; Haplotype; LD; LOD; MAF; PCR; PM; Polymerase Chain Reaction; SNP; Tibetan; UM; UTR; base pair(s); bp; cytochrome P450; deoxyribonucleic acid; extensive metabolizer; linkage disequilibrium; log odds score; min; minor allele frequency; minute; poor metabolizer; s; second; single nucleotide polymorphisms; ultra-rapid metabolizer; untranslated region(s).