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, Akira Saito, Naohiko MasakiMichiyasu Yagura, Yukio Watanabe, Yoko Nakamura, Koichi Honda, Yoshinobu Fukushima, Masaaki Shimada, Noboru Hirashima, Masakazu Kobayashi, Yukio Ohara, Tatsuji Komatsu, Hajime Ota, Hiroshi Kohno, Hirotaka Kouno, Haruhiro Yamashita, Takeaki Sato, Toshiki Komeda, Michiaki Koga, Masahiko Takahashi, Tetsuo Yamamoto, Kazuhiro Sugi, Michio Kato, Eiichi Takezaki, Hiroshi Mano, Hideo Nishimura, Eiji Mita, Hironori Sakai, Shinya Nagaoka, Seigo Abiru, Koji Yano

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)676-686
Number of pages11
JournalJournal of gastroenterology
Volume46
Issue number5
DOIs
Publication statusPublished - May 2011

All Science Journal Classification (ASJC) codes

  • Gastroenterology

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