title: Genetic variation in metabolizing enzyme and transporter genes: comprehensive assessment in 3 major East Asian subpopulations with comparison to Caucasians and Africans.
abstract: The advent of high-throughput technologies has proven valuable in the assessment of genetic differences and their effects on drug activation, metabolism, disposition, and transport. However, most studies to date have focused on a small number of genes or few alleles, some of which are rare and therefore observed infrequently or lacked rigorous ethnic characterization, thus reducing the ability to extrapolate within and among populations. In this study, the authors comprehensively assessed the allele frequencies of 165 variants comprising 27 drug-metabolizing enzyme and transporter (DMET) genes from 2188 participants across 3 major ethnic populations: Caucasians, Africans, and East Asians. This sample size was sufficiently large to demonstrate genetic differences among these major ethnic groups while concomitantly confirming similarities among East Asian subpopulations (Korean, Han Chinese, and Japanese). A comprehensive presentation of allele and genotype frequencies is included in the online supplement, and 3 of the most widely studied cytochrome P450 (CYP) genes, CYP2D6, CYP2C19, and CYP2C9; 2 non-CYP enzymes, NAT1 and TMPT; and 2 transporter genes, SLCO1B1 and SLCO2B1, are presented herein according to ethnic classification.
authors.affiliation: Discovery and Development Statistics, Eli Lilly and Company, Lilly Corporate Center DC 2026, Indianapolis, IN 46285, USA. manmi@lilly.com
authors.forename: Michael
authors.initials: M
authors.lastname: Man
authors.forename: Mark
authors.initials: M
authors.lastname: Farmen
authors.forename: Carmen
authors.initials: C
authors.lastname: Dumaual
authors.forename: Choo Hua
authors.initials: CH
authors.lastname: Teng
authors.forename: Brian
authors.initials: B
authors.lastname: Moser
authors.forename: Shin
authors.initials: S
authors.lastname: Irie
authors.forename: Gyu Jeong
authors.initials: GJ
authors.lastname: Noh
authors.forename: Reuben
authors.initials: R
authors.lastname: Njau
authors.forename: Sandra
authors.initials: S
authors.lastname: Close
authors.forename: Stephen
authors.initials: S
authors.lastname: Wise
authors.forename: Richard
authors.initials: R
authors.lastname: Hockett
mesh_terms: D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D044466:Asian People; D044383:Black People; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D027381:Liver-Specific Organic Anion Transporter 1; D008780:Methyltransferases / Q000235:genetics*; D027361:Organic Anion Transporters / Q000235:genetics*; D044465:White People
chemical_list: D007527:Isoenzymes; D027381:Liver-Specific Organic Anion Transporter 1; D027361:Organic Anion Transporters; C503999:SLCO1B1 protein, human; C450859:SLCO2B1 protein, human; D003577:Cytochrome P-450 Enzyme System; D008780:Methyltransferases; C022745:thiopurine methyltransferase; D001191:Arylamine N-Acetyltransferase; C089384:N-acetyltransferase 1