Screening of Genetic Polymorphisms of <em>CYP3A4</em> and <em>CYP3A5</em> Genes

Screening of Genetic Polymorphisms of <em>CYP3A4</em> and <em>CYP3A5</em> Genes

Given the <em>CYP3A4</em> and <em>CYP3A5</em>’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 <em>CYP3A4</em>/5 polymorphisms and compare the genotype distributions among five ethnicities. To identify <em>CYP3A4</em>/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 <em>CYP3A5</em>*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 <em>CYP3A5</em> (+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.