Comparison of genetic variation in drug ADME-related genes in Thais with Caucasian, African and Asian HapMap populations
Comparison of genetic variation in drug ADME-related genes in Thais with Caucasian, African and Asian HapMap populations
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DOI：
10.1038/jhg.2015.115
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发表时间：
2016-02-01
影响因子：
3.5
通讯作者：
Chantratita, Wasun
中科院分区：
文献类型：
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作者：
Jittikoon, Jiraphun;Mahasirimongkol, Surakameth;Chantratita, Wasun
本研究的目的是调查泰国人群中药物吸收、分布、代谢和消除（ADME）相关基因的等位基因频率，并将这些基因与HapMap人群进行比较，包括高加索人（CEU）、非洲人（YRI）和亚洲人（CHB/JPT）。采用药物代谢酶和转运蛋白（DMET）加基因分型系统研究了190名泰国人药物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相和II相药物代谢酶、药物转运蛋白和其他参与ADME过程的基因中具有功能和临床意义。将泰国人的基因分型数据与其他HapMap人群（包括高加索人、非洲人和亚洲人）的分布进行比较。结果表明，在5个群体中，有43个SNPs具有统计学意义。然而，只有26个SNP在泰国与CEU和泰国与CHB/JPT之间的成对比较中显示出统计学显著性。这26个SNPs分别属于13组药物ADME相关基因，即CYP 2A 6、CYP 3A 5、CYP 2B 6、CYP 2C 8、CYP 2C 9、CYP 2C 19、CYP 2D 6、VKORC 1、COMT、NAT 2、TPMT、UGT 1A 1和SLCO 1B 1。这些基因表现出临床意义，如先前在许多研究中观察到的。结果可以解释药物的药代动力学和药效学在泰国人的基础上药物ADME相关基因的遗传变异在这篇文章中强调的临床变异。
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.