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 journalArticle

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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 1 2011

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Biliary Liver Cirrhosis
Integrins
Genes
Liver Transplantation
Single Nucleotide Polymorphism
Liver Failure
Genetic Polymorphisms
DNA Sequence Analysis
Restriction Fragment Length Polymorphisms
Freezing
Liver Diseases
Healthy Volunteers
Japan
Fibrosis

All Science Journal Classification (ASJC) codes

  • Gastroenterology

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A polymorphism in the integrin αv subunit gene affects the progression of primary biliary cirrhosis in Japanese patients. / 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; Saito, Akira; Masaki, Naohiko; Yagura, Michiyasu; Watanabe, Yukio; Nakamura, Yoko; Honda, Koichi; Fukushima, Yoshinobu; Shimada, Masaaki; Hirashima, Noboru; Kobayashi, Masakazu; Ohara, Yukio; Komatsu, Tatsuji; Ota, Hajime; Kohno, Hiroshi; Kouno, Hirotaka; Yamashita, Haruhiro; Sato, Takeaki; Komeda, Toshiki; Koga, Michiaki; Takahashi, Masahiko; Yamamoto, Tetsuo; Sugi, Kazuhiro; Kato, Michio; Takezaki, Eiichi; Mano, Hiroshi; Nishimura, Hideo; Mita, Eiji; Sakai, Hironori; Nagaoka, Shinya; Abiru, Seigo; Yano, Koji.

In: Journal of gastroenterology, Vol. 46, No. 5, 01.05.2011, p. 676-686.

Research output: Contribution to journalArticle

Inamine, T, Nakamura, M, Kawauchi, A, Shirakawa, Y, Hashiguchi, H, Aiba, Y, Taketomi, A, Shirabe, K, Nakamuta, M, Hayashi, S, Saoshiro, T, Komori, A, Yatsuhashi, H, Kondo, S, Omagari, K, Maehara, Y, Ishibashi, H, Tsukamoto, K, Saito, A, Masaki, N, Yagura, M, Watanabe, Y, Nakamura, Y, Honda, K, Fukushima, Y, Shimada, M, Hirashima, N, Kobayashi, M, Ohara, Y, Komatsu, T, Ota, H, Kohno, H, Kouno, H, Yamashita, H, Sato, T, Komeda, T, Koga, M, Takahashi, M, Yamamoto, T, Sugi, K, Kato, M, Takezaki, E, Mano, H, Nishimura, H, Mita, E, Sakai, H, Nagaoka, S, Abiru, S & Yano, K 2011, 'A polymorphism in the integrin αv subunit gene affects the progression of primary biliary cirrhosis in Japanese patients', Journal of gastroenterology, vol. 46, no. 5, pp. 676-686. https://doi.org/10.1007/s00535-010-0351-0
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 ; Saito, Akira ; Masaki, Naohiko ; Yagura, Michiyasu ; Watanabe, Yukio ; Nakamura, Yoko ; Honda, Koichi ; Fukushima, Yoshinobu ; Shimada, Masaaki ; Hirashima, Noboru ; Kobayashi, Masakazu ; Ohara, Yukio ; Komatsu, Tatsuji ; Ota, Hajime ; Kohno, Hiroshi ; Kouno, Hirotaka ; Yamashita, Haruhiro ; Sato, Takeaki ; Komeda, Toshiki ; Koga, Michiaki ; Takahashi, Masahiko ; Yamamoto, Tetsuo ; Sugi, Kazuhiro ; Kato, Michio ; Takezaki, Eiichi ; Mano, Hiroshi ; Nishimura, Hideo ; Mita, Eiji ; Sakai, Hironori ; Nagaoka, Shinya ; Abiru, Seigo ; Yano, Koji. / A polymorphism in the integrin αv subunit gene affects the progression of primary biliary cirrhosis in Japanese patients. In: Journal of gastroenterology. 2011 ; Vol. 46, No. 5. pp. 676-686.
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title = "A polymorphism in the integrin αv subunit gene affects the progression of primary biliary cirrhosis in Japanese patients",
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.",
author = "Tatsuo Inamine and Minoru Nakamura and Ayumi Kawauchi and Yayoi Shirakawa and Hisae Hashiguchi and Yoshihiro Aiba and Akinobu Taketomi and Ken Shirabe and Makoto Nakamuta and Shigeki Hayashi and Takeo Saoshiro and Atsumasa Komori and Hiroshi Yatsuhashi and Shinji Kondo and Katsuhisa Omagari and Yoshihiko Maehara and Hiromi Ishibashi and Kazuhiro Tsukamoto and Akira Saito and Naohiko Masaki and Michiyasu Yagura and Yukio Watanabe and Yoko Nakamura and Koichi Honda and Yoshinobu Fukushima and Masaaki Shimada and Noboru Hirashima and Masakazu Kobayashi and Yukio Ohara and Tatsuji Komatsu and Hajime Ota and Hiroshi Kohno and Hirotaka Kouno and Haruhiro Yamashita and Takeaki Sato and Toshiki Komeda and Michiaki Koga and Masahiko Takahashi and Tetsuo Yamamoto and Kazuhiro Sugi and Michio Kato and Eiichi Takezaki and Hiroshi Mano and Hideo Nishimura and Eiji Mita and Hironori Sakai and Shinya Nagaoka and Seigo Abiru and Koji Yano",
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T1 - A polymorphism in the integrin αv subunit gene affects the progression of primary biliary cirrhosis in Japanese patients

AU - Inamine, Tatsuo

AU - Nakamura, Minoru

AU - Kawauchi, Ayumi

AU - Shirakawa, Yayoi

AU - Hashiguchi, Hisae

AU - Aiba, Yoshihiro

AU - Taketomi, Akinobu

AU - Shirabe, Ken

AU - Nakamuta, Makoto

AU - Hayashi, Shigeki

AU - Saoshiro, Takeo

AU - Komori, Atsumasa

AU - Yatsuhashi, Hiroshi

AU - Kondo, Shinji

AU - Omagari, Katsuhisa

AU - Maehara, Yoshihiko

AU - Ishibashi, Hiromi

AU - Tsukamoto, Kazuhiro

AU - Saito, Akira

AU - Masaki, Naohiko

AU - Yagura, Michiyasu

AU - Watanabe, Yukio

AU - Nakamura, Yoko

AU - Honda, Koichi

AU - Fukushima, Yoshinobu

AU - Shimada, Masaaki

AU - Hirashima, Noboru

AU - Kobayashi, Masakazu

AU - Ohara, Yukio

AU - Komatsu, Tatsuji

AU - Ota, Hajime

AU - Kohno, Hiroshi

AU - Kouno, Hirotaka

AU - Yamashita, Haruhiro

AU - Sato, Takeaki

AU - Komeda, Toshiki

AU - Koga, Michiaki

AU - Takahashi, Masahiko

AU - Yamamoto, Tetsuo

AU - Sugi, Kazuhiro

AU - Kato, Michio

AU - Takezaki, Eiichi

AU - Mano, Hiroshi

AU - Nishimura, Hideo

AU - Mita, Eiji

AU - Sakai, Hironori

AU - Nagaoka, Shinya

AU - Abiru, Seigo

AU - Yano, Koji

PY - 2011/5/1

Y1 - 2011/5/1

N2 - 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.

AB - 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.

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U2 - 10.1007/s00535-010-0351-0

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JO - Journal of Gastroenterology

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