title: Genetic polymorphisms and haplotypes of por, encoding cytochrome p450 oxidoreductase, in a Japanese population.
abstract: Cytochrome P450 oxidoreductase (POR) transfers electrons from NADPH to all microsomal cytochrome P450 (CYP) enzymes and is necessary for microsomal CYP activities. In this study, to find genetic variations and to elucidate the haplotype structures of POR, we comprehensively screened the genetic variations in the 5'-flanking region, all the exons and their flanking introns of POR for 235 Japanese subjects. Seventy-five genetic variations including 26 novel ones were found: 7 were in the 5'-flanking region, 2 in the 5'-untranslated region (5'-UTR, non-coding exon 1), 16 in the coding exons (10 nonsynonymous and 6 synonymous), 45 in the introns, 4 in the 3'-UTR and 1 in the 3'-flanking region. Of these, 4 novel nonsynonymous variations, 86C>T (T29M), 1648C>T (R550W), 1708C>T (R570C) and 1975G>A (A659T), were detected with allele frequencies of 0.002. We also detected known nonsynonymous SNPs 683C>T (P228L), 1237G>A (G413S), 1453G>A (A485T), 1508C>T (A503V), 1510G>A (G504R) and 1738G>C (E580Q) with frequencies of 0.002, 0.009, 0.002, 0.434, 0.002 and 0.002, respectively. Based on the linkage disequilibrium (LD) profiles, the analyzed region could be divided into two LD blocks. For Blocks 1 and 2, 14 and 46 haplotypes were inferred, respectively, and 2 and 6 common haplotypes found in more than 0.03 frequencies accounted for more than 81% of the inferred haplotypes. This study provides fundamental and useful information for the pharmacogenetic studies of drugs metabolized by CYPs in the Japanese population.
authors.affiliation: Project team for Pharmacogenetics, National Institute of Health Sciences,Tokyo, Japan. yoshiro@nihs.go.jp
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Saito
authors.forename: Noboru
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Noriko
authors.initials: N
authors.lastname: Katori
authors.forename: Keiko
authors.initials: K
authors.lastname: Maekawa
authors.forename: Hiromi
authors.initials: H
authors.lastname: Fukushima-Uesaka
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sugimoto
authors.forename: Kouichi
authors.initials: K
authors.lastname: Kurose
authors.forename: Kimie
authors.initials: K
authors.lastname: Sai
authors.forename: Nahoko
authors.initials: N
authors.lastname: Kaniwa
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Sawada
authors.forename: Hideo
authors.initials: H
authors.lastname: Kunitoh
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Ohe
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Yoshida
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Matsumura
authors.forename: Nagahiro
authors.initials: N
authors.lastname: Saijo
authors.forename: Haruhiro
authors.initials: H
authors.lastname: Okuda
authors.forename: Tomohide
authors.initials: T
authors.lastname: Tamura
mesh_terms: D020121:5' Untranslated Regions; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D005091:Exons; D006239:Haplotypes; D006801:Humans; D007438:Introns; D015810:Linkage Disequilibrium; D009251:NADPH-Ferrihemoprotein Reductase / Q000235:genetics*; D011110:Polymorphism, Genetic
chemical_list: D020121:5' Untranslated Regions; D009251:NADPH-Ferrihemoprotein Reductase