Association analysis of cytotoxic T-lymphocyte antigen 4 gene polymorphisms with primary biliary cirrhosis in Japanese patients

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概要

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• Background & Aims: Primary biliary cirrhosis (PBC) is an organ-specific autoimmune disease of still unidentified genetic etiology that is characterized by chronic inflammation of the liver. Since cytotoxic T-lymphocyte antigen 4 (CTLA4) polymorphisms have recently been linked with PBC susceptibility in studies on Caucasians, we investigated the genetic association between CTLA4 polymorphisms and PBC in a Japanese population. Methods: Five single nucleotide polymorphisms (SNPs) in the CTLA4 gene (rs733618, rs5742909, rs231775, rs3087243, and rs231725) were genotyped in 308 patients with PBC and 268 healthy controls using a TaqMan assay. Results: One CTLA4 gene SNP (rs231725) was significantly associated with susceptibility to anti-mitochondrial antibody (AMA)-positive PBC, but clinical significance disappeared after correction for multiple testing. Moreover, CTLA4 gene SNPs did not influence AMA development or disease progression to orthotopic liver transplantation in our Japanese cohort. In haplotype analyses, one haplotype [haplotype 1 (CGGA)] at rs5742909, rs231775, rs3087243, and rs231725, was significantly associated with susceptibility to both AMA-positive PBC and overall PBC. Conclusions: This study showed that CTLA4 gene polymorphisms had a modest, but significant association with susceptibility to PBC in the Japanese population. The connection between genetic variants and the function of the CTLA4 gene remains to be addressed in future investigations.

• ELSEVIER SCIENCE BVの論文

著者

• Ida H

  First Department Of Internal Medicine Nagasaki University Hospital Of Medicine And Dentistry Graduat

• Nakamuta Makoto

  九州大学 医学系学府病態制御内科学

• Nakamuta M

  The Department Of Medicine And Bioregulatory Science Graduate School Of Medical Sciences Kyushu Univ

• Nakamuta Makoto

  九州大学 医学研究院病態制御内科学分野

• Makita Naomasa

  Department Of Gastroenterology National Hospital Organization Kyushu Medical Center

• Umemura Takeji

  信州大学 医学部内科学

• Tanaka Eiji

  Shinshu Univ. School Of Medicine Matsumoto Jpn

• Nakashima M

  鳥取大学 医学系研究科遺伝子医療学

• OTA Masao

  Department of Legal Medicine, Shinshu University School of Medicine

• Ota Masao

  Department Of Legal Medicine Shinshu University School Of Medicine

• Takeda Naokazu

  Department Of Gastroenterology Shinshu University School Of Medicine

• Nakamuta Makoto

  Department Of Gastroenterology National Hospital Organization Kyushu Medical Center

• Umemura Takeji

  Department Of Gastroenterology Shinshu University School Of Medicine

• Yoshizawa Kaname

  Department Of Gastroenterology Shinshu University School Of Medicine

• Umemura Takeji

  信州大学 医学部病態解析診断

• Joshita Satoru

  Department Of Gastroenterology Shinshu University School Of Medicine

• Tanaka Eiji

  Division Of Gastroenterology Department Of Internal Medicine Shinshu University School Of Medicine

• Nakamura Minoru

  Clinical Research Center National Hospital Organization (nho) Nagasaki Medical Center

• Tanaka E

  Department Of Medicine Shinshu University School Of Medicine

• Joshita Satoru

  Department of Legal Medicine, Shinshu University School of Medicine

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