Jittikoon Jiraphun, Mahasirimongkol Surakameth, Charoenyingwattana Angkana, Chaikledkaew Usa, Tragulpiankit Pramote, Mangmool Supachoke, Inunchot Wimala, Somboonyosdes Chayapol, Wichukchinda Nuanjun, Sawanpanyalert Pathom, He Yijing, McLeod Howard L, Chantratita Wasun
Department of Biochemistry, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand.
Medical Genetic Center, Medical Life Science Institute, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand.
J Hum Genet. 2016 Feb;61(2):119-27. doi: 10.1038/jhg.2015.115. Epub 2015 Oct 1.
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.
本研究的目的是调查泰国人群中药物吸收、分布、代谢和排泄（ADME）相关基因的等位基因频率，并将这些基因与包括高加索人（CEU）、非洲人（YRI）和亚洲人（CHB/JPT）在内的HapMap人群进行比较。使用药物代谢酶和转运体（DMET）加基因分型系统研究了190名泰国人的药物ADME相关基因的遗传变异。我们检测了225个基因的1936个单核苷酸多态性（SNP），这些基因在I期和II期药物代谢酶、药物转运体以及参与ADME过程的其他基因中具有已记录的功能和临床意义。将泰国人的基因分型数据分布与其他HapMap人群（包括高加索人、非洲人和亚洲人群）进行了比较。分析表明，在五个人群之间比较有43个SNP具有统计学意义。然而，在泰国人与CEU以及泰国人与CHB/JPT的成对比较中，只有26个SNP显示出统计学意义。这26个SNP属于13组药物ADME相关基因，即CYP2A6、CYP3A5、CYP2B6、CYP2C8、CYP2C9、CYP2C19、CYP2D6、VKORC1、COMT、NAT2、TPMT、UGT1A1和SLCO1B1。这些基因如先前在许多研究中所观察到的那样具有临床意义。本文强调的结果可以基于药物ADME相关基因的遗传变异来解释泰国人药物药代动力学和药效学的临床变异性。
