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

Sojeong Yi, Hyungmi An, Howard Lee, Sangin Lee, Ichiro Ieiri, Youngjo Lee, Joo Youn Cho, Takeshi Hirota, Masato Fukae, Kenji Yoshida, Shinichiro Nagatsuka, Miyuki Kimura, Shin Irie, Yuichi Sugiyama, Dong Wan Shin, Kyoung Soo Lim, Jae Yong Chung, Kyung Sang Yu, In Jin Jang

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

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.

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.

Original languageEnglish
Pages (from-to)477-485
Number of pages9
JournalPharmacogenetics and Genomics
Volume24
Issue number10
DOIs
StatePublished - 10 Oct 2014

Bibliographical note

Publisher Copyright:
© 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Keywords

  • Drug-metabolizing enzymes and transporters microarray
  • East Asian
  • Ethnic difference
  • Pharmacogenetics

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