title: Genetic polymorphisms of OCT-1 confer susceptibility to severe progression of primary biliary cirrhosis in Japanese patients.
abstract: BACKGROUND
  To identify the genetic factors involved in the pathogenesis of primary biliary cirrhosis (PBC), we focused on the organic cation transporter 1 (OCT1/SLC22A1), which is closely associated with phosphatidylcholine synthesis in hepatocytes.
  
  
  METHODS
  We selected four (rs683369, rs2282143, rs622342 and rs1443844) OCT-1 single nucleotide polymorphisms (SNPs), and genotyped these SNPs using the TaqMan probe method in 275 Japanese PBC patients and 194 gender-matched, healthy volunteers as controls.
  
  
  RESULTS
  The Chi-square test revealed that the rs683369 variant allele (G) was associated with insusceptibility to PBC development [P = 0.009, odds ratio (OR) 0.60, 95 % confidence interval (CI) 0.40-0.88] in an allele model, and that the rs683369 variant allele (G) was associated with jaundice-type progression in a minor allele dominant genotype model (P = 0.032, OR 3.10, 95 % CI 1.05-9.14). The OCT-1 rs2282143 variant (T) and rs622342 variant (C) were also associated with jaundice-type progression in a minor allele recessive genotype model (P = 0.0002, OR 10.58, 95 % CI 2.36-47.54, and P = 0.006, OR 7.84, 95 % CI 1.39-44.36, respectively). Furthermore, the association of OCT-1 rs683369 and rs622342 with susceptibility to jaundice-type progression was confirmed by a replication study with a distinct set of PBC patients who underwent liver transplantation.
  
  
  CONCLUSIONS
  The present study is the first report on the association of OCT-1 genetic polymorphisms with the overall development and jaundice-type progression of PBC.
authors.affiliation: Department of Pharmacy, Clinical Research Institute, National Hospital Organization (NHO) Kyushu Medical Center, 1-8-1 Jigyouhama, Fukuoka, 810-8563, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Ohishi
authors.forename: Makoto
authors.initials: M
authors.lastname: Nakamuta
authors.forename: Naoko
authors.initials: N
authors.lastname: Ishikawa
authors.forename: Ohki
authors.initials: O
authors.lastname: Saitoh
authors.forename: Hitomi
authors.initials: H
authors.lastname: Nakamura
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Aiba
authors.forename: Atsumasa
authors.initials: A
authors.lastname: Komori
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Migita
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yatsuhashi
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Fukushima
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Kohjima
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Yoshimoto
authors.forename: Kunitaka
authors.initials: K
authors.lastname: Fukuizumi
authors.forename: Makoto
authors.initials: M
authors.lastname: Ishibashi
authors.forename: Takashi
authors.initials: T
authors.lastname: Nishino
authors.forename: Ken
authors.initials: K
authors.lastname: Shirabe
authors.forename: Akinobu
authors.initials: A
authors.lastname: Taketomi
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Maehara
authors.forename: Hiromi
authors.initials: H
authors.lastname: Ishibashi
authors.forename: Minoru
authors.initials: M
authors.lastname: Nakamura
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007564:Japan; D007565:Jaundice / Q000209:etiology / Q000235:genetics*; D008105:Liver Cirrhosis, Biliary / Q000150:complications / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D027702:Organic Cation Transporter 1 / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: D027702:Organic Cation Transporter 1