Authors: 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
Publish Date: 2010/12/01
Volume: 46, Issue: 5, Pages: 676-686
Abstract
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 PBCIn the primary study eight tag single nucleotide polymorphisms SNPs in ITGAV were analyzed by polymerase chain reaction PCRrestriction fragment length polymorphism direct DNA sequencing or highresolution 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 gendermatched healthy Japanese volunteers control subjects For the replication study 35 PBC patients who progressed to endstage hepatic failure and underwent liver transplantation PBC cohort II were also analyzedThree 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 endstage hepatic failure in the replication study of PBC patients who underwent liver transplantation PBC cohort IIITGAV is a genetic determinant for the severe progression of PBC in Japanese patients Genetic polymorphisms of ITGAV may be useful for identifying highrisk Japanese PBC patients including those who will require liver transplantation at the time of initial diagnosisThis study was supported by Health and Labour Sciences Research Grants for Research on Measures for Intractable Diseases from the Ministry of Health Labour and Welfare of Japan M Nakamura a GrantinAid for Scientific Research C KAKENHI No 20590545 from the Ministry of Education Culture Sports Science and Technology of Japan K Omagari and the president’s discretionary fund of Nagasaki University Japan K Tsukamoto The authors thank the PBC patients and healthy volunteers for participating in this study and also thank members of the PBC Study Group in NHSOLJ Dr Akira Saito NHO Nishisaitama Chuo Hospital Dr Naohiko Masaki Kokusai Medical Center Dr Michiyasu Yagura NHO Tokyo Hospital Drs Yukio Watanabe and Yoko Nakamura NHO Sagamihara Hospital Drs Koichi Honda and Toyokichi Muro NHO Oita Medical Center Dr Yoshinobu Fukushima NHO Kyushu Medical Center Drs Masaaki Shimada and Noboru Hirashima NHO Nagoya Medical Center Dr Masakazu Kobayashi NHO Matsumoto Medical Center Dr Yukio Ohara NHO Hokkaido Medical Center Dr Tatsuji Komatsu NHO Yokohama Medical Center Dr Hajime Ota NHO Kanazawa Medical Center Drs Hiroshi Kohno and Hirotaka Kouno NHO Kure Medical Center Dr Haruhiro Yamashita NHO Okayama Medical Center Dr Takeaki Sato NHO Kokura Medical Center Dr Toshiki Komeda NHO Kyoto Medical Center Dr Michiaki Koga NHO Ureshino Medical Center Dr Masahiko Takahashi NHO Tokyo Medical Center Dr Tetsuo Yamamoto NHO Yonago Medical Center Dr Kazuhiro Sugi NHO Kumamoto Medical Center Dr Michio Kato NHO Minami Wakayama Medical Center Dr Eiichi Takezaki NHO Higashi Hiroshima Medical Center Dr Hiroshi Mano NHO Sendai Medical Center Dr Hideo Nishimura NHO Douhoku Hospital Dr Eiji Mita NHO Osaka Medical Center Dr Hironori Sakai NHO Beppu Medical Center and Drs Shinya Nagaoka Seigo Abiru and Koji Yano NHO Nagasaki Medical Center for providing blood samples and clinical information from PBC patients
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