Journal of Gastroenterology

, Volume 46, Issue 5, pp 676–686

A polymorphism in the integrin αV subunit gene affects the progression of primary biliary cirrhosis in Japanese patients

  • Tatsuo Inamine
  • Minoru Nakamura
  • Ayumi Kawauchi
  • Yayoi Shirakawa
  • Hisae Hashiguchi
  • Yoshihiro Aiba
  • Akinobu Taketomi
  • Ken Shirabe
  • Makoto Nakamuta
  • Shigeki Hayashi
  • Takeo Saoshiro
  • Atsumasa Komori
  • Hiroshi Yatsuhashi
  • Shinji Kondo
  • Katsuhisa Omagari
  • Yoshihiko Maehara
  • Hiromi Ishibashi
  • Kazuhiro Tsukamoto
  • the PBC Study Group in NHOSLJ
Original Article—Liver, Pancreas, and Biliary Tract

DOI: 10.1007/s00535-010-0351-0

Cite this article as:
Inamine, T., Nakamura, M., Kawauchi, A. et al. J Gastroenterol (2011) 46: 676. doi:10.1007/s00535-010-0351-0

Abstract

Background

Accumulating evidence indicates that multiple genetic factors are involved in the pathogenesis of primary biliary cirrhosis (PBC). The aim of this study was to investigate whether polymorphisms of the integrin αV subunit gene (ITGAV), a component of integrin αVβ6, which plays an important role in the process of fibrosis, are associated with susceptibility to the onset and/or progression of PBC.

Methods

In the primary study, eight tag single nucleotide polymorphisms (SNPs) in ITGAV were analyzed by polymerase chain reaction (PCR)-restriction fragment length polymorphism, direct DNA sequencing, or high-resolution melting curve analysis in 309 Japanese patients with PBC who were registered in the National Hospital Organization Study Group for Liver Disease in Japan (PBC cohort I) and 293 gender-matched healthy Japanese volunteers (control subjects). For the replication study, 35 PBC patients who progressed to end-stage hepatic failure and underwent liver transplantation (PBC cohort II) were also analyzed.

Results

Three tag SNPs (rs3911238, rs10174098, and rs1448427) in ITGAV were significantly associated with the severe progression of PBC, but not with susceptibility to the onset of PBC, in the primary study (PBC cohort I). Among these SNPs, rs1448427 was also significantly associated with the severe progression to end-stage hepatic failure in the replication study of PBC patients who underwent liver transplantation (PBC cohort II).

Conclusions

ITGAV is a genetic determinant for the severe progression of PBC in Japanese patients. Genetic polymorphisms of ITGAV may be useful for identifying high-risk Japanese PBC patients, including those who will require liver transplantation, at the time of initial diagnosis.

Keywords

PBC Integrin αV Hepatic fibrosis Premature ductopenia Progression 

Copyright information

© Springer 2010

Authors and Affiliations

  • Tatsuo Inamine
    • 1
  • Minoru Nakamura
    • 2
    • 3
    • 4
  • Ayumi Kawauchi
    • 1
  • Yayoi Shirakawa
    • 1
  • Hisae Hashiguchi
    • 1
  • Yoshihiro Aiba
    • 2
  • Akinobu Taketomi
    • 5
  • Ken Shirabe
    • 5
  • Makoto Nakamuta
    • 4
  • Shigeki Hayashi
    • 4
  • Takeo Saoshiro
    • 4
  • Atsumasa Komori
    • 2
    • 3
  • Hiroshi Yatsuhashi
    • 2
    • 3
  • Shinji Kondo
    • 1
  • Katsuhisa Omagari
    • 6
  • Yoshihiko Maehara
    • 5
  • Hiromi Ishibashi
    • 2
    • 3
  • Kazuhiro Tsukamoto
    • 1
  • the PBC Study Group in NHOSLJ
  1. 1.Department of PharmacotherapeuticsNagasaki University Graduate School of Biomedical SciencesNagasakiJapan
  2. 2.Clinical Research Center, National Hospital Organization (NHO) Nagasaki Medical CenterOmuraJapan
  3. 3.Department of HepatologyNagasaki University Graduate School of Biomedical SciencesNagasakiJapan
  4. 4.Headquarters of PBC Research in the National Hospital Organization Study Group for Liver Disease in Japan (NHOSLJ)NagasakiJapan
  5. 5.Department of Surgery and Science, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
  6. 6.Department of Nutrition, Faculty of Nursing and NutritionSiebold University of NagasakiNagasakiJapan

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