Screening of Genetic Polymorphisms of CYP3A4 and CYP3A5 Genes

• 영문명: Screening of Genetic Polymorphisms of CYP3A4 and CYP3A5 Genes
• 발행기관: 대한생리학회-대한약리학회
• 저자명: Jin Sol Lee Hyun Sub Cheong Lyoung Hyo Kim Ji On Kim Doo Won Seo Young Hoon Kim Myeon Woo Chung Soon
• 간행물 정보: 『The Korean Journal of Physiology & Pharmacology』제17권 제6호, 479~484쪽, 전체 6쪽
• 주제분류: 의약학 > 의학일반
• 파일형태: PDF
• 발행일자: 2013.01.01

영문 초록

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 phar-macogenetic 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.

키워드

CYP3A4 CYP3A5 Cytochrome P450 Pharmacogenetics SNP