title: Genetic variations and frequencies of major haplotypes in SLCO1B1 encoding the transporter OATP1B1 in Japanese subjects: SLCO1B1*17 is more prevalent than *15.
abstract: A liver-specific transporter organic anion transporting polypeptide 1B1 (OATP1B1, also known as OATP-C) is encoded by SLCO1B1 and mediates uptake of various endogenous and exogenous compounds from blood into hepatocytes. In this study, 15 SLCO1B1 exons (including non-coding exon 1) and their flanking introns were comprehensively screened for genetic variations in 177 Japanese subjects. Sixty-two genetic variations, including 28 novel ones, were found: 7 in the 5'-flanking region, 1 in the 5'-untranslated region (UTR), 13 in the coding exons (9 nonsynonymous and 4 synonymous variations), 5 in the 3'-UTR, and 36 in the introns. Five novel nonsynonymous variations, 311T>A (Met104Lys), 509T>C (Met170Thr), 601A>G (Lys201Glu), 1553C>T (Ser518Leu), and 1738C>T (Arg580Stop), were found as heterozygotes. The allele frequencies were 0.008 for 1738C>T (Arg580Stop) and 0.003 for the four other variations. Arg580Stop having a stop codon at codon 580 results in loss of half of transmembrane domain (TMD) 11, TMD12, and a cytoplasmic tail, which might affect transport activity. In addition, novel variations, IVS12-1G>T at the splice acceptor site and -3A>C in the Kozak motif, were detected at 0.003 and 0.014 frequencies, respectively. Haplotype analysis using -11187G>A, -3A>C, IVS12-1G>T and 9 nonsynonymous variations revealed that the haplotype frequencies for (*)1b, (*)5, (*)15, and (*)17 were 0.469, 0.000 (not detected), 0.037, and 0.133, respectively. These data would provide fundamental and useful information for pharmacogenetic studies on OATP1B1-transported drugs in Japanese.
authors.affiliation: Project Team for Pharmacogenetics, National Institute of Health Sciences, Tokyo, Japan.
authors.forename: Su-Ryang
authors.initials: SR
authors.lastname: Kim
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Saito
authors.forename: Kimie
authors.initials: K
authors.lastname: Sai
authors.forename: Kouichi
authors.initials: K
authors.lastname: Kurose
authors.forename: Keiko
authors.initials: K
authors.lastname: Maekawa
authors.forename: Nahoko
authors.initials: N
authors.lastname: Kaniwa
authors.forename: Shogo
authors.initials: S
authors.lastname: Ozawa
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Kamatani
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Shirao
authors.forename: Noboru
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hamaguchi
authors.forename: Hideo
authors.initials: H
authors.lastname: Kunitoh
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Ohe
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Yamada
authors.forename: Tomohide
authors.initials: T
authors.lastname: Tamura
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Yoshida
authors.forename: Hironobu
authors.initials: H
authors.lastname: Minami
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ohtsu
authors.forename: Nagahiro
authors.initials: N
authors.lastname: Saijo
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Sawada
mesh_terms: D024506:5' Flanking Region; D020121:5' Untranslated Regions; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D018388:Codon, Terminator; D004252:DNA Mutational Analysis; D005091:Exons; D005787:Gene Frequency; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D007438:Introns; D007564:Japan; D027381:Liver-Specific Organic Anion Transporter 1; D008969:Molecular Sequence Data; D027361:Organic Anion Transporters / Q000235:genetics* / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000378:metabolism; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide
chemical_list: D020121:5' Untranslated Regions; D018388:Codon, Terminator; D027381:Liver-Specific Organic Anion Transporter 1; D027361:Organic Anion Transporters; D004364:Pharmaceutical Preparations; C503999:SLCO1B1 protein, human