title: Genetic variations and haplotype structures of the ABCB1 gene in a Japanese population: an expanded haplotype block covering the distal promoter region, and associated ethnic differences.
abstract: As functional ABCB1 haplotypes were recently reported in the promoter region of the gene, we resequenced the ABCB1 distal promoter region, along with other regions (the enhancer and proximal promoter regions, and all 28 exons), in a total of 533 Japanese subjects. Linkage disequilibrium (LD) analysis based on 92 genetic variations revealed 4 LD blocks with the same make up as previously described (Blocks -1, 1, 2 and 3), except that Block 1 was expanded to include the distal promoter region, and that a new linkage between polymorphisms -1,789G>A in the distal promoter region and IVS5 + 123A>G in intron 5 was identified. We re-assigned Block 1 haplotypes, and added novel haplotypes to the other 3 blocks. The reported promoter haplotypes were further classified into several types according to tagging variations within Block 1 coding or intronic regions. Our current data reconfirm the haplotype profiles of the other three blocks, add more detailed information on functionally-important haplotypes in Block 1 and 2 in the Japanese population, and identified differences in haplotype profiles between ethnic groups. Our updated analysis of ABCB1 haplotype blocks will assist pharmacogenetic and disease-association studies carried out using Asian subjects.
authors.affiliation: Project Team for Pharmacogenetics, National Institute of Health Sciences, Tokyo, 158-8501, USA. sai@nihs.go.jp
authors.forename: K
authors.initials: K
authors.lastname: Sai
authors.forename: M
authors.initials: M
authors.lastname: Itoda
authors.forename: Y
authors.initials: Y
authors.lastname: Saito
authors.forename: K
authors.initials: K
authors.lastname: Kurose
authors.forename: N
authors.initials: N
authors.lastname: Katori
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: H
authors.initials: H
authors.lastname: Tomoike
authors.forename: S
authors.initials: S
authors.lastname: Kamakura
authors.forename: M
authors.initials: M
authors.lastname: Kitakaze
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: Y
authors.initials: Y
authors.lastname: Yamada
authors.forename: Y
authors.initials: Y
authors.lastname: Ohe
authors.forename: Y
authors.initials: Y
authors.lastname: Shimada
authors.forename: K
authors.initials: K
authors.lastname: Shirao
authors.forename: H
authors.initials: H
authors.lastname: Minami
authors.forename: A
authors.initials: A
authors.lastname: Ohtsu
authors.forename: T
authors.initials: T
authors.lastname: Yoshida
authors.forename: N
authors.initials: N
authors.lastname: Saijo
authors.forename: N
authors.initials: N
authors.lastname: Kamatani
authors.forename: S
authors.initials: S
authors.lastname: Ozawa
authors.forename: J
authors.initials: J
authors.lastname: Sawada
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D005006:Ethnicity / Q000235:genetics*; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D007564:Japan; D015810:Linkage Disequilibrium / Q000235:genetics; D009369:Neoplasms / Q000453:epidemiology / Q000235:genetics; D027361:Organic Anion Transporters / Q000235:genetics*; D011401:Promoter Regions, Genetic; D017180:Tachycardia, Ventricular / Q000453:epidemiology / Q000235:genetics
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D027361:Organic Anion Transporters