Genetic polymorphisms of OCT-1 confer susceptibility to severe progression of primary biliary cirrhosis in Japanese patients

• DOI: 10.1007/s00535-013-0795-0
• Publication Date: 2013-04-30T21:12:04Z
• Authors: Yuki Ohishi; Makoto Nakamuta; Naoko Ishikawa; Ohki Saitoh; Hitomi Nakamura; Yoshihiro Aiba; Atsumasa Komori; Kiyoshi Migita; Hiroshi Yatsuhashi; Nobuyoshi Fukushima; Motoyuki Kohjima; Tsuyoshi Yoshimoto; Kunitaka Fukuizumi; Makoto Ishibashi; Takashi Nishino; Ken Shirabe; Akinobu Taketomi; Yoshihiko Maehara; Hiromi Ishibashi; Minoru Nakamura
• Keywords: Adult; Male; 0301 basic medicine; Genotype; Liver Cirrhosis, Biliary; Organic Cation Transporter 1; Jaundice; Middle Aged; Polymorphism, Single Nucleotide; 3. Good health; 03 medical and health sciences; Japan; Case-Control Studies; Disease Progression; Humans; Female; Genetic Predisposition to Disease; Aged

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.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.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.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.