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

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 importa...

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Published in:Journal of gastroenterology 2011-05, Vol.46 (5), p.676-686
Main Authors: Inamine, Tatsuo, Nakamura, Minoru, Kawauchi, Ayumi, Shirakawa, Yayoi, Hashiguchi, Hisae, Aiba, Yoshihiro, Taketomi, Akinobu, Shirabe, Ken, Nakamuta, Makoto, Hayashi, Shigeki, Saoshiro, Takeo, Komori, Atsumasa, Yatsuhashi, Hiroshi, Kondo, Shinji, Omagari, Katsuhisa, Maehara, Yoshihiko, Ishibashi, Hiromi, Tsukamoto, Kazuhiro
Format: Article
Language:English
Subjects:
Abdominal Surgery
Adult
Aged
Asian Continental Ancestry Group - genetics
Biliary Tract
Case-Control Studies
Colorectal Surgery
Disease Progression
End Stage Liver Disease - etiology
End Stage Liver Disease - genetics
End Stage Liver Disease - therapy
Female
Gastroenterology
Genetic Predisposition to Disease
Hepatology
Humans
Integrin alphaV - genetics
Japan
Liver Cirrhosis, Biliary - genetics
Liver Transplantation
Male
Medicine
Medicine & Public Health
Middle Aged
Original Article—Liver
Pancreas
Polymorphism, Restriction Fragment Length
Polymorphism, Single Nucleotide
Sequence Analysis, DNA
Surgical Oncology
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Summary: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.
ISSN:0944-1174
1435-5922
DOI:10.1007/s00535-010-0351-0