title: Genetic polymorphisms of UGT1A6 in a Japanese population.
abstract: Thirteen single nucleotide polymorphisms (SNPs), including 6 novel ones, were found in exon 1 and its flanking region of UDP-glucuronosyltransferase (UGT) 1A6 from 195 Japanese subjects. Several novel SNPs were identified, including 269G>A (R90H), 279A>G (S93S), and 308C>A (S103X) in exon 1, and IVS1+109C>T, IVS1+120A>G, and IVS1+142C>T in the intron downstream of exon 1. Among these SNPs, 308C>A confers termination of translation at codon 103, resulting in the production of an immature protein that probably lacks enzymatic activity. The allele frequencies were 0.003 for all the 6 SNPs. In addition, the 3 known nonsynonymous SNPs were detected: 19T>G (S7A), 541A>G (T181A), and 552A>C (R184S) with frequencies of 0.226, 0.218, and 0.226, respectively. High linkage disequilibrium was observed among 19T>G (S7A), 315A>G (L105L), 541A>G (T181A), 552A>C (R184S), and IVS1+130G>T, as reported in Caucasian and African-American populations. Then, 11 haplotypes in UGT1A6 were estimated. The novel nonsynonymous variant, 269A or 308A, was shown to be located on the same DNA strand together with 19G, 315G, 541G, 552C, and IVS1+130T. Our results provide fundamental and useful information for genotyping UGT1A6 in the Japanese, and probably Asian populations.
authors.affiliation: Project Team for Pharmacogenetics, National Institute of Health Sciences, Tokyo, Japan.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Saeki
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Saito
authors.forename: Hideto
authors.initials: H
authors.lastname: Jinno
authors.forename: Kimie
authors.initials: K
authors.lastname: Sai
authors.forename: Nahoko
authors.initials: N
authors.lastname: Kaniwa
authors.forename: Shogo
authors.initials: S
authors.lastname: Ozawa
authors.forename: Kazuo
authors.initials: K
authors.lastname: Komamura
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kotake
authors.forename: Hideki
authors.initials: H
authors.lastname: Morishita
authors.forename: Shiro
authors.initials: S
authors.lastname: Kamakura
authors.forename: Masafumi
authors.initials: M
authors.lastname: Kitakaze
authors.forename: Hitonobu
authors.initials: H
authors.lastname: Tomoike
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Shirao
authors.forename: Hironobu
authors.initials: H
authors.lastname: Minami
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ohtsu
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Yoshida
authors.forename: Nagahiro
authors.initials: N
authors.lastname: Saijo
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Kamatani
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Sawada
mesh_terms: D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D017931:DNA Primers; D005787:Gene Frequency; D014644:Genetic Variation; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D007438:Introns / Q000235:genetics; D007564:Japan; D020641:Polymorphism, Single Nucleotide
chemical_list: D017931:DNA Primers; C110655:UDP-glucuronosyltransferase, UGT1A6; D014453:Glucuronosyltransferase