title: Haplotype structures of the UGT1A gene complex in a Japanese population.
abstract: Genetic polymorphisms of UDP-glucuronosyltransferases (UGTs) are involved in individual and ethnic differences in drug metabolism. To reveal co-occurrence of the UGT1A polymorphisms, we first analyzed haplotype structures of the entire UGT1A gene complex using the polymorphisms from 196 Japanese subjects. Based on strong linkage disequilibrium between UGT1A8 and 1A10, among 1A9, 1A7, and 1A6, and between 1A3 and 1A1, the complex was divided into five blocks, Block 8/10, Block 9/6, Block 4, Block 3/1, and Block C, and the haplotypes for each block were subsequently determined/inferred. Second, using pyrosequencing or direct sequencing, additional 105 subjects were genotyped for 41 functionally tagged polymorphisms. The data from 301 subjects confirmed the robustness of block partitioning, but several linkages among the haplotypes with functional changes were found across the blocks. Thus, important haplotypes and their linkages were identified among the UGT1A gene blocks (and segments), which should be considered in pharmacogenetic studies.
authors.affiliation: Project Team for Pharmacogenetics, National Institute of Health Sciences, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Saeki
authors.forename: Y
authors.initials: Y
authors.lastname: Saito
authors.forename: H
authors.initials: H
authors.lastname: Jinno
authors.forename: K
authors.initials: K
authors.lastname: Sai
authors.forename: S
authors.initials: S
authors.lastname: Ozawa
authors.forename: K
authors.initials: K
authors.lastname: Kurose
authors.forename: N
authors.initials: N
authors.lastname: Kaniwa
authors.forename: K
authors.initials: K
authors.lastname: Komamura
authors.forename: T
authors.initials: T
authors.lastname: Kotake
authors.forename: H
authors.initials: H
authors.lastname: Morishita
authors.forename: S
authors.initials: S
authors.lastname: Kamakura
authors.forename: M
authors.initials: M
authors.lastname: Kitakaze
authors.forename: H
authors.initials: H
authors.lastname: Tomoike
authors.forename: K
authors.initials: K
authors.lastname: Shirao
authors.forename: T
authors.initials: T
authors.lastname: Tamura
authors.forename: N
authors.initials: N
authors.lastname: Yamamoto
authors.forename: H
authors.initials: H
authors.lastname: Kunitoh
authors.forename: T
authors.initials: T
authors.lastname: Hamaguchi
authors.forename: T
authors.initials: T
authors.lastname: Yoshida
authors.forename: K
authors.initials: K
authors.lastname: Kubota
authors.forename: A
authors.initials: A
authors.lastname: Ohtsu
authors.forename: M
authors.initials: M
authors.lastname: Muto
authors.forename: H
authors.initials: H
authors.lastname: Minami
authors.forename: N
authors.initials: N
authors.lastname: Saijo
authors.forename: N
authors.initials: N
authors.lastname: Kamatani
authors.forename: J-I
authors.initials: JI
authors.lastname: Sawada
mesh_terms: D044466:Asian People / Q000235:genetics*; D014453:Glucuronosyltransferase / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide; D000099148:UGT1A1 Enzyme
chemical_list: D014453:Glucuronosyltransferase; D000099148:UGT1A1 Enzyme