Genetic Landscape of VIP Pharmacogenomic Variants in the Kinh Vietnamese Population.

Abstract

Background: Genetic polymorphisms in the genes encoding enzymes and proteins in drug metabolism, transport, and response can significantly impact enzymatic activity and overall pharmacokinetics and pharmacodynamics, leading to inter-individual and inter-population differences in drug efficacy and safety. The prevalence of pharmacogenomic variants often differs among populations due to unique evolutionary and demographic factors. By studying the genetic variation within 100 pharmacogenes in the Kinh Vietnamese population, a relatively underexplored group in pharmacogenomic research, we aim to provide insights into the population-specific pharmacogenomic landscape.

Materials and methods: 100 healthy people were recruited for peripheral blood donation after getting consents. Genomic DNA from participants was sequenced at coding regions of 100 pharmacogenes. Sequence reads were qualified, and variants were called using Genome analysis toolkit (GATK) followed with variant processing. Very important variants were characterized. Genetic distance using pairwise fixation index and allele frequencies comparison between the Kinh population and 25 populations of the 1000 Genome Project were analyzed.

Results: 689 variants were called with 652 SNPs and 37 indels including 371 missense-, 266 synonymous-, 30 frameshift-, 14 stop-gain-, 2 stop-lost-, 3 in-frame insertion-, 2 in-frame deletion- and 1 protein variant. There are 59 novel variants (8.6%) present in 39/100 genes in which 13 variants are labeled with damaging phenotype. 28 VIP variants were obtained from these regions. Allele frequencies of variants are mostly similar with East Asians, but different from Africans. Remarkably, variants rs1801280 and rs1208 (NAT2), rs2231142 (ABCG2), rs2306283 (SCLO1B1) and rs4148323 (UGT1A1) distribute significantly between Kinh people and all other populations.

Conclusion: The prevalence of pharmacogenomic variants of 100 pharmacogenes was obtained for Kinh Vietnamese people, in which 28 variants were characterized as very important variants. Kinh Vietnamese shows close genetic distance with East Asians but far from Africans. The variants with distinguished distribution in Kinh people were also highlighted.