Journal of Gastroenterology

, Volume 49, Issue 2, pp 332–342

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

  • 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
  • PBC Study Group of NHOSLJ
Original Article—Liver, Pancreas, and Biliary Tract

DOI: 10.1007/s00535-013-0795-0

Cite this article as:
Ohishi, Y., Nakamuta, M., Ishikawa, N. et al. J Gastroenterol (2014) 49: 332. doi:10.1007/s00535-013-0795-0

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.

Keywords

PBC OCT-1 Genetic polymorphism Phosphatidylcholine Hepatic failure Progression 

Copyright information

© Springer Japan 2013

Authors and Affiliations

  • Yuki Ohishi
    • 1
  • Makoto Nakamuta
    • 2
  • Naoko Ishikawa
    • 1
  • Ohki Saitoh
    • 1
  • Hitomi Nakamura
    • 3
  • Yoshihiro Aiba
    • 3
  • Atsumasa Komori
    • 3
    • 4
  • Kiyoshi Migita
    • 3
    • 4
  • Hiroshi Yatsuhashi
    • 3
    • 4
  • Nobuyoshi Fukushima
    • 2
  • Motoyuki Kohjima
    • 2
  • Tsuyoshi Yoshimoto
    • 2
  • Kunitaka Fukuizumi
    • 2
  • Makoto Ishibashi
    • 5
  • Takashi Nishino
    • 1
  • Ken Shirabe
    • 6
  • Akinobu Taketomi
    • 6
  • Yoshihiko Maehara
    • 6
  • Hiromi Ishibashi
    • 3
    • 4
  • Minoru Nakamura
    • 3
    • 4
    • 7
  • PBC Study Group of NHOSLJ
  1. 1.Department of Pharmacy, Clinical Research InstituteNational Hospital Organization (NHO) Kyushu Medical CenterFukuokaJapan
  2. 2.Department of Gastroenterology, Clinical Research InstituteNational Hospital Organization (NHO) Kyushu Medical CenterFukuokaJapan
  3. 3.Clinical Research CenterNational Hospital Organization (NHO) Nagasaki Medical CenterOmuraJapan
  4. 4.Department of HepatologyNagasaki University Graduate School of Biomedical SciencesOmuraJapan
  5. 5.Department of Pharmaceutical and Health Care Management, Faculty of Pharmaceutical SciencesFukuoka UniversityFukuokaJapan
  6. 6.Department of Surgery and ScienceKyushu University Graduate School of Medical SciencesFukuokaJapan
  7. 7.Headquarters of PBC Research in the NHO Study Group for Liver Disease in Japan (NHOSLJ)NagasakiJapan

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