title: Direct sequencing and comprehensive screening of genetic polymorphisms on CYP2 family genes (CYP2A6, CYP2B6, CYP2C8, and CYP2E1) in five ethnic populations.
abstract: Recently, CYP2A6, CYP2B6, CYP2C8, and CYP2E1 have been reported to play a role in the metabolic effect of pharmacological and carcinogenic compounds. Moreover, genetic variations of drug metabolism genes have been implicated in the interindividual variation in drug disposition and pharmacological response. To define the distribution of single nucleotide polymorphisms (SNPs) in these four CYP2 family genes and to discover novel SNPs across ethnic groups, 288 DNAs composed of 48 African-Americans, 48 European-Americans, 48 Japanese, 48 Han Chinese, and 96 Koreans were resequenced. A total of 143 SNPs, 26 in CYP2A6, 45 in CYP2B6, 29 in CYP2C8, and 43 in CYP2E1, were identified, including 13 novel variants. Notably, two SNPs in the regulatory regions, a promoter SNP rs2054675 and a nonsynonymous rs3745274 (p.172Q>H) in CYP2B6, showed significantly different minor allele frequencies (MAFs) among ethnic groups (minimum P = 4.30 × 10(-12)). In addition, rs2031920 in the promoter region of CYP2E1 showed a wide range of MAF between different ethnic groups, and even among other various ethnic groups based on public reports. Among 13 newly discovered SNPs in this study, 5 SNPs were estimated to have potential functions in further in silico analyses. Some differences in genetic variations and haplotypes of CYP2A6, CYP2B6, CYP2C8, and CYP2E1 were observed among populations. Our findings could be useful in further researches, such as genetic associations with drug responses.
authors.affiliation: Department of Life Science, Sogang University, Seoul, Republic of Korea.
authors.forename: Jeong-Hyun
authors.initials: JH
authors.lastname: Kim
authors.forename: Hyun Sub
authors.initials: HS
authors.lastname: Cheong
authors.forename: Byung Lae
authors.initials: BL
authors.lastname: Park
authors.forename: Lyoung Hyo
authors.initials: LH
authors.lastname: Kim
authors.forename: Hee Jung
authors.initials: HJ
authors.lastname: Shin
authors.forename: Han Sung
authors.initials: HS
authors.lastname: Na
authors.forename: Myeon Woo
authors.initials: MW
authors.lastname: Chung
authors.forename: Hyoung Doo
authors.initials: HD
authors.lastname: Shin
mesh_terms: D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D065637:Cytochrome P-450 CYP2A6 / Q000235:genetics*; D065702:Cytochrome P-450 CYP2B6 / Q000235:genetics*; D065727:Cytochrome P-450 CYP2C8 / Q000235:genetics*; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics*; D005006:Ethnicity / Q000235:genetics*; D005787:Gene Frequency / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics
chemical_list: D019392:Cytochrome P-450 CYP2E1; D001189:Aryl Hydrocarbon Hydroxylases; C585710:CYP2A6 protein, human; C585599:CYP2B6 protein, human; C450259:CYP2C8 protein, human; D065637:Cytochrome P-450 CYP2A6; D065702:Cytochrome P-450 CYP2B6; D065727:Cytochrome P-450 CYP2C8