title: Screening of Genetic Polymorphisms of CYP3A4 and CYP3A5 Genes.
abstract: Given the CYP3A4 and CYP3A5's impact on the efficacy of drugs, the genetic backgrounds of individuals and populations are regarded as an important factor to be considered in the prescription of personalized medicine. However, genetic studies with Korean population are relatively scarce compared to those with other populations. In this study, we aimed to identify CYP3A4/5 polymorphisms and compare the genotype distributions among five ethnicities. To identify CYP3A4/5 SNPs, we first performed direct sequencing with 288 DNA samples which consisted of 96 Koreans, 48 European-Americans, 48 African-Americans, 48 Han Chinese, and 48 Japanese. The direct sequencing identified 15 novel SNPs, as well as 42 known polymorphisms. We defined the genotype distributions, and compared the allele frequencies among five ethnicities. The results showed that minor allele frequencies of Korean population were similar with those of the Japanese and Han Chinese populations, whereas there were distinct differences from European-Americans or African-Americans. Among the pharmacogenetic markers, frequencies of CYP3A4*1B (rs2740574) and CYP3A5*3C (rs776742) in Asian groups were different from those in other populations. In addition, minor allele frequency of CYP3A4*18 (rs28371759) was the highest in Korean population. Additional in silico analysis predicted that two novel non-synonymous SNPs in CYP3A5 (+27256C>T, P389S and +31546T>G, I488S) could alter protein structure. The frequency distributions of the identified polymorphisms in the present study may contribute to the expansion of pharmacogenetic knowledge.
authors.affiliation: Department of Life Science, Sogang University, Seoul 121-742, Korea.
authors.forename: Jin Sol
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Department of Genetic Epidemiology, SNP Genetics, Inc., Seoul 121-742, Korea.
authors.forename: Hyun Sub
authors.initials: HS
authors.lastname: Cheong
authors.affiliation: Department of Genetic Epidemiology, SNP Genetics, Inc., Seoul 121-742, Korea.
authors.forename: Lyoung Hyo
authors.initials: LH
authors.lastname: Kim
authors.affiliation: Department of Genetic Epidemiology, SNP Genetics, Inc., Seoul 121-742, Korea.
authors.forename: Ji On
authors.initials: JO
authors.lastname: Kim
authors.affiliation: Clinical Research Division, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Osong Health Technology Administration Complex, Osong 363-700, Korea.
authors.forename: Doo Won
authors.initials: DW
authors.lastname: Seo
authors.affiliation: Clinical Research Division, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Osong Health Technology Administration Complex, Osong 363-700, Korea.
authors.forename: Young Hoon
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Clinical Research Division, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Osong Health Technology Administration Complex, Osong 363-700, Korea.
authors.forename: Myeon Woo
authors.initials: MW
authors.lastname: Chung
authors.affiliation: Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Osong Health Technology Administration Complex, Osong 363-700, Korea.
authors.forename: Soon Young
authors.initials: SY
authors.lastname: Han
authors.affiliation: Department of Life Science, Sogang University, Seoul 121-742, Korea. ; Department of Genetic Epidemiology, SNP Genetics, Inc., Seoul 121-742, Korea.
authors.forename: Hyoung Doo
authors.initials: HD
authors.lastname: Shin
keywords: CYP3A4; CYP3A5; Cytochrome P450; Pharmacogenetics; SNP