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Title: Comparison of genetic variation in drug ADME-related genes in Thais with Caucasian, African and Asian HapMap populations
Authors: Jiraphun Jittikoon
Surakameth Mahasirimongkol
Angkana Charoenyingwattana
Usa Chaikledkaew
Pramote Tragulpiankit
Supachoke Mangmool
Wimala Inunchot
Chayapol Somboonyosdes
Nuanjun Wichukchinda
Pathom Sawanpanyalert
Yijing He
Howard L. Mcleod
Wasun Chantratita
Mahidol University
Thailand Ministry of Public Health
Faculty of Medicine, Ramathibodi Hospital, Mahidol University
The University of North Carolina at Chapel Hill
Keywords: Biochemistry, Genetics and Molecular Biology
Issue Date: 1-Feb-2016
Citation: Journal of Human Genetics. Vol.61, No.2 (2016), 119-127
Abstract: © 2016 The Japan Society of Human Genetics. The objectives of this study are to investigate allele frequencies of drug absorption, distribution, metabolism and elimination (ADME)-related genes in the Thai population and to compare these genes to HapMap populations including Caucasians (CEU), Africans (YRI) and Asians (CHB/JPT). Genetic variations of drug ADME-related genes in 190 Thais were investigated using drug metabolizing enzymes and transporters (DMET) plus genotyping system. We examined 1936 single nucleotide polymorphisms (SNPs) of 225 genes that have documented functional and clinical significances in phase I and phase II drug metabolism enzymes, drug transporters and other genes involved in ADME processes. Distributions of genotyping data from Thai were compared with other HapMap populations including Caucasian, African and Asian populations. The analysis demonstrated 43 SNPs with statistical significance comparing among five populations. However, only 26 SNPs showed statistical significance in pair-wise comparisons between Thai versus CEU and Thai versus CHB/JPT. These 26 SNPs belong to 13 groups of drug ADME-related genes which are CYP2A6, CYP3A5, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, VKORC1, COMT, NAT2, TPMT, UGT1A1 and SLCO1B1. These genes demonstrated clinical significances as previously observed in many studies. The results could explain clinical variability in pharmacokinetics and pharmacodynamics of drugs in Thais based on genetic variations in drug ADME-related gene emphasized in this article.
ISSN: 1435232X
Appears in Collections:Scopus 2016-2017

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