title: Comparison of genetic variation in drug ADME-related genes in Thais with Caucasian, African and Asian HapMap populations.
abstract: 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.
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand.
authors.forename: Jiraphun
authors.initials: J
authors.lastname: Jittikoon
authors.affiliation: Medical Genetic Center, Medical Life Science Institute, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand.
authors.forename: Surakameth
authors.initials: S
authors.lastname: Mahasirimongkol
authors.affiliation: Pharmacogenomics Project under collaboration between Ramathibodi Hospital and Thailand Center of Excellence for Life Sciences, Bangkok, Thailand.
authors.forename: Angkana
authors.initials: A
authors.lastname: Charoenyingwattana
authors.affiliation: Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand.
authors.forename: Usa
authors.initials: U
authors.lastname: Chaikledkaew
authors.affiliation: Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand.
authors.forename: Pramote
authors.initials: P
authors.lastname: Tragulpiankit
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand.
authors.forename: Supachoke
authors.initials: S
authors.lastname: Mangmool
authors.affiliation: Medical Genetic Center, Medical Life Science Institute, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand.
authors.forename: Wimala
authors.initials: W
authors.lastname: Inunchot
authors.affiliation: Medical Genetic Center, Medical Life Science Institute, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand.
authors.forename: Chayapol
authors.initials: C
authors.lastname: Somboonyosdes
authors.affiliation: Medical Genetic Center, Medical Life Science Institute, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand.
authors.forename: Nuanjun
authors.initials: N
authors.lastname: Wichukchinda
authors.affiliation: Medical Genetic Center, Medical Life Science Institute, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand.
authors.forename: Pathom
authors.initials: P
authors.lastname: Sawanpanyalert
authors.affiliation: UNC Institute for Pharmacogenomics and Individualized Therapy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Yijing
authors.initials: Y
authors.lastname: He
authors.affiliation: UNC Institute for Pharmacogenomics and Individualized Therapy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Howard L
authors.initials: HL
authors.lastname: McLeod
authors.affiliation: Department of Pathology, Faculty of Medicine, Ramathibodhi Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Wasun
authors.initials: W
authors.lastname: Chantratita
mesh_terms: D044466:Asian People / Q000235:genetics; D044383:Black People / Q000235:genetics; D005787:Gene Frequency; D060148:HapMap Project; D006801:Humans; D008658:Inactivation, Metabolic / Q000235:genetics; D026901:Membrane Transport Proteins / Q000235:genetics; D000071184:Pharmacogenomic Variants; D020641:Polymorphism, Single Nucleotide; D013785:Thailand; D044465:White People / Q000235:genetics
chemical_list: D026901:Membrane Transport Proteins