Genetic Polymorphism Analysis Of Cytochrome P450 2D6 In Chinese Tibetan Population

Pharmacogenetics is a study of how genetic polymorphism related to drug metabolism works with drug efficacy. Cytochrome P450 super family is the important phasel drug metabolizing enzyme which involves in the metabolism of many endogenous and exogenous substrates. CYP2D6 exists in the liver, metabolizes up to 20%-25% of the prescribed drugs including many neuroleptic, anti-arrhythmic, analgesics, antidepressants, antiemetics and anticancer drugs.The enzyme activity of C YP2D6 would be influenced by a lot of factors, such as genetic differences, ages, physical conditions and life style, ect. Polymorphism of the gene coding CYP2D6 can lead to different levels expressions of enzyme activity, completely loss, decrease or increase which affects the metabolism of drugs. More than 70 different alleles of CYP2D6 have been described up to date, the common alleles decreasing the enzyme activity greatly are CYP2D6*10, CYP2D6* and CYP2D6*41. For the Asian groups, allele CYP2D6*10 is the most common one which contains two point mutations explaining the main cause of intermediate metabolizers among the yellow-skinned people, while it is rarely found in the Caucasians. Therefore, studying of CYP2D6 polymorphism is clinically helpful to evaluate drug safety and efficacy, and then provide a theory basis for pharmcogenetic research.There have been some studies on the polymorphism of CYP2D6 in the Chinese Han population. China is a nation of great land mass and large population. Tibetan, as one of the minorities, some of the important gene polymorphic sites may vary with Chinese Han population. In this study, we systematically screened the polymorphisms of the whole CYP2D6 gene, including the 5'flanking region, all exons, and all introns, in the Chinese Tibetan, sample of 95 healthy subjects from the Tibet autonomous region.The results of this study:In Chinese Tibetan population, a total of 51 different genetic polymorphisms were detected in the CYP2D6 gene, including 12 novle ones; We analyzed the CYP2D6 alleles and genotype frequencies, the main alleles were CYP2D6*1, CYP2D6*2, CYP2D6*10, CYP2D6*34 and CYP2D6*41, the most frequent alleles were the allele*1,*2 and*10, occur at frequencies of 31.4,30.4and 33.6%, respectively; We investigated the LD pattern and haplotype construction of this gene in this population by Haploview; We also compared frequencies of CYP2D6 alleles and genotypes with those of other national and ethnic populations, the results indicate significant differences in different populations.This study is the first one which takes a fully analysis on the genetic polymorphism of CYP2D6 in the Chinese Tibetan and helps build a database of CYP2D6 alleles and genotype frequency among minorities as well as provides a theory basis for eventually individualized therapy.