Genetic polymorphisms of the drug-metabolizing enzyme cytochrome P450 2A6 in a Tibetan Chinese population.

Detection of CYP2A6 variant alleles, and knowledge about their allelic frequency in Tibetan ethnic groups, is important to establish the clinical relevance of screening for these polymorphisms to optimize pharmacotherapy. We used DNA sequencing to investigate the promoter, exons and surrounding introns, and untranslated region of the CYP2A6 gene in 100 unrelated healthy Tibetan individuals. We also used SIFT and PolyPhen-2 to predict the protein function of the novel non-synonymous mutation in CYP2A6 coding regions. We found 33 different CYP2A6 polymorphisms in the Tibetan population, five of which were novel: -98T > G in promoter region, 1886C > A, 5640C > A, 5827G > T in intron and missense mutation 5011G > A in exon 7. We identified six CYP2A6 alleles (*1, *10, *11, *14, *15 and *18), with a wide frequency range from 1.00% to 86.50% in the population. We also detected six CYP2A6 genotypes, with a wide frequency range from 2.00% to 73.00%. Three of which (*1/*10, *1/*11 and *1/*18) lead to decreased enzyme activity. This study provided new information regarding CYP2A6genetic polymorphisms in Tibetan individuals, which will greatly facilitate studies on the relevance of pharmacogenetics for CYP2A6 with respect to disease risk and to the pharmacokinetics and pharmacodynamics of many drugs.