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Pharmacogenet Genomics. 2014 Oct;24(10):477-85. doi: 10.1097/FPC.0000000000000075.

Korean, Japanese, and Chinese populations featured similar genes encoding drug-metabolizing enzymes and transporters: a DMET Plus microarray assessment.

Author information

1
aDepartment of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital bDepartment of Statistics, Seoul National University cDepartment of Statistics, Ewha University, Seoul, Korea dDepartment of Clinical Pharmacokinetics, Graduate School of Pharmaceutical Sciences, Kyushu University eKyushu Clinical Pharmacology Research Clinic, Fukuoka fADME&Tox Research Institute, Sekisui Medical Co. Ltd, Ibaraki gSugiyama Laboratory, RIKEN Innovation Center RIKEN Research Cluster for Innovation, Yokohama Bio Industry Center, Yokohama, Japan.

Abstract

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.

PMID:
25029633
DOI:
10.1097/FPC.0000000000000075
[Indexed for MEDLINE]

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