Korean, Japanese, and Chinese populations featured similar genes encoding drug-metabolizing enzymes and transporters: a DMET Plus microarray assessment SoJeong Yi a , Hyungmi An a,b , Howard Lee a , Sangin Lee b , Ichiro Ieiri d , Youngjo Lee b , Joo-Youn Cho a , Takeshi Hirota d , Masato Fukae d , Kenji Yoshida f , Shinichiro Nagatsuka f , Miyuki Kimura e , Shin Irie e , Yuichi Sugiyama g , Dong Wan Shin c , Kyoung Soo Lim a , Jae-Yong Chung a , Kyung-Sang Yu a and In-Jin Jang a Background Interethnic differences in genetic polymorphism in genes encoding drug-metabolizing enzymes and transporters are one of the major factors that cause ethnic differences in drug response. This study aimed to investigate genetic polymorphisms in genes involved in drug metabolism, transport, and excretion among Korean, Japanese, and Chinese populations, the three major East Asian ethnic groups. Methods The frequencies of 1936 variants representing 225 genes encoding drug-metabolizing enzymes and transporters were determined from 786 healthy participants (448 Korean, 208 Japanese, and 130 Chinese) using the Affymetrix Drug-Metabolizing Enzymes and Transporters Plus microarray. To compare allele or genotype frequencies in the high-dimensional data among the three East Asian ethnic groups, multiple testing, principal component analysis (PCA), and regularized multinomial logit model through least absolute shrinkage and selection operator were used. Results On microarray analysis, 1071 of 1936 variants (>50% of markers) were found to be monomorphic. In a large number of genetic variants, the fixation index and Pearson’s correlation coefficient of minor allele frequencies were less than 0.034 and greater than 0.95, respectively, among the three ethnic groups. PCA identified 47 genetic variants with multiple testing, but was unable to discriminate ethnic groups by the first three components. Multinomial least absolute shrinkage and selection operator analysis identified 269 genetic variants that showed different frequencies among the three ethnic groups. However, none of those variants distinguished between the three ethnic groups during subsequent PCA. Conclusion Korean, Japanese, and Chinese populations are not pharmacogenetically distant from one another, at least with regard to drug disposition, metabolism, and elimination. Pharmacogenetics and Genomics 24:477–485 © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins. Pharmacogenetics and Genomics 2014, 24:477–485 Keywords: Drug-Metabolizing Enzymes and Transporters microarray, East Asian, ethnic difference, pharmacogenetics a Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, b Department of Statistics, Seoul National University, c Department of Statistics, Ewha University, Seoul, Korea, d Department of Clinical Pharmacokinetics, Graduate School of Pharmaceutical Sciences, Kyushu University, e Kyushu Clinical Pharmacology Research Clinic, Fukuoka, f ADME&Tox Research Institute, Sekisui Medical Co. Ltd, Ibaraki and g Sugiyama Laboratory, RIKEN Innovation Center RIKEN Research Cluster for Innovation, Yokohama Bio Industry Center, Yokohama, Japan Correspondence to In-Jin Jang, MD, PhD, Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Korea Tel: + 82 2 740 8290; fax: + 82 2 742 9252; e-mail: ijjang@snu.ac.kr Present address: SoJeong Yi: Department of Clinical Pharmacology, Dong-A University Hospital, Busan, 602-715, Korea Received 1 January 2014 Accepted 4 June 2014 Introduction In 1998, the International Conference on Harmonization (ICH) E5 guideline, entitled ‘Ethnic Factors in the Acceptability of Foreign Clinical Data’, was issued to adequately evaluate the influence of ethnic factors on the clinical efficacy and safety of drugs, and to minimize duplication of clinical studies [1]. However, the accept- ability of foreign clinical data to a native population has been challenging because the ICH guideline requires clinical data that can bridge the pharmacoki- netic, pharmacodynamic, and safety information between regions [2]. There is evidence that East Asians, including Korean, Japanese, and Chinese populations, exhibit similarities in genetics, and that they share some common environ- mental characteristics (e.g. the social and cultural aspects of medical practice, diet) [3,4]. However, regulatory agencies in these three countries believe that clinical data obtained from other East Asian populations still fall short Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (www.pharmacogeneticsandgenomics.com). Original article 477 1744-6872 © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins DOI: 10.1097/FPC.0000000000000075 Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.