Deciphering DMET genetic data: comprehensive assessment of Northwestern Han, Tibetan, Uyghur populations and their comparison to eleven 1000 genome populations

Abstract

We investigated the allele frequencies of drug absorption, distribution, metabolism and elimination (ADME)-related drug-metabolizing enzymes and transporters (DMET) genes in the Northwestern Han, Tibetan and Uyghur populations and compared the related genes in these three populations with those in eleven 1000 Genome populations. We examined 1936 single nucleotide polymorphisms of 225 DMET genes involved in ADME processes and found 732, 679 and 804 sites were polymorphic in Han, Tibetan and Uyghur. Tibetan differed from Han in only four sites (p < .05), whereas Uyghur differed from Han and Tibetan in 24 and 21 sites, respectively (p < .05). The distributions of 1058 genotyping data of 245 individuals from Han, Tibetan and Uyghur were compared with 1207 other individuals from the eleven 1000 Genomes populations. The top four populations in Han that exhibited the smallest pairwise Fst values were CHB, Tibetan, CHD and JPT; those in Tibetan were Han, CHB, Uyghur and CHD; and those in Uyghur were Han, Tibetan, GIH and CEU. MEGA results revealed that CHB, CHD, JPT, Han, Tibetan and Uyghur were grouped in cluster 1. GIH, MEX, CEU and TSI were grouped in cluster 2. MKK, ASW, LWK and YRI were grouped in cluster 3.

Genetic Polymorphism of Drug Metabolic Gene CYPs, VKORC1, NAT2, DPYD and CHST3 of Five Ethnic Minorities in Heilongjiang Province, Northeast China

“…From SNP database, PharmGKB database and published literature, 2,23 relatively important SNPs related to drug metabolism were screened according to the following principles: First, Very Important Pharmacogenes (VIP) variants in PharmGKB database were searched. We screened out clinically relevant variants with a high level of clinical annotation.…”