caa a22 4500 445888520 CHVBK 20180317145607.0 cr unu---uuuuu 170323e20111001xx s 000 0 eng 10.1007/s00535-011-0417-7 doi (NATIONALLICENCE)springer-10.1007/s00535-011-0417-7 Genetic polymorphisms in CTLA4 and SLC4A2 are differentially associated with the pathogenesis of primary biliary cirrhosis in Japanese patients [Elektronische Daten] [Yoshihiro Aiba, Minoru Nakamura, Satoru Joshita, Tatsuo Inamine, Atsumasa Komori, Kaname Yoshizawa, Takeji Umemura, Hitomi Horie, Kiyoshi Migita, Hiroshi Yatsuhashi, Makoto Nakamuta, Nobuyoshi Fukushima, Takeo Saoshiro, Shigeki Hayashi, Hiroshi Kouno, Hajime Ota, Toyokichi Muro, Yukio Watanabe, Yoko Nakamura, Toshiki Komeda, Masaaki Shimada, Naohiko Masaki, Tatsuji Komatsu, Michiyasu Yagura, Kazuhiro Sugi, Michiaki Koga, Kazuhiro Tsukamoto, Eiji Tanaka, Hiromi Ishibashi] Background: Anti-gp210 and anti-centromere antibodies are different risk factors for the progression of primary biliary cirrhosis (PBC). In order to dissect the genetic basis for the production of these autoantibodies, as well as the development and progression of PBC in Japanese patients, we examined single nucleotide polymorphisms (SNPs) in cytotoxic T-lymphocyte antigen 4 (CTLA4) and solute carrier family 4 anion exchanger, member 2 (SLC4A2), which have been associated with the pathogenesis of PBC in Caucasian patients. Methods: Four SNPs for both CTLA4 and SLC4A2 were genotyped, using the polymerase chain reaction-restriction fragment length polymorphism method and TaqMan assay, in 450 Japanese PBC patients and 371 sex-matched healthy controls. Results: The CTLA4 rs231775, rs3087243, and rs231725 SNPs were significantly associated with PBC susceptibility. The CTLA4 rs231725 SNP was significantly associated with progression to late-stage disease. The CTLA-4 haplotype 1 (rs231775 G, rs231777 C, rs3087243 G, rs231725 A; GCGA) was a risk factor for PBC susceptibility but a protective factor for PBC progression. Conversely, the CTLA-4 haplotype 2 (ACAG) was a protective and risk factor, respectively, for PBC susceptibility and progression. In addition, the CTLA4 rs231777 SNP and haplotype 3 (ATGG) was significantly associated with anti-gp210 antibody production, while SLC4A2 haplotype 4 (rs2069443 A, rs2303933 G, rs2303937 A, rs2303941 T; AGAT) and haplotype 3 (AAGC) were significantly associated with PBC susceptibility and anti-centromere antibody production, respectively. Conclusions: CTLA4 and SLC4A2 genetic polymorphisms are differentially associated with PBC development and progression, as well as anti-gp210 or anti-centromere antibody production, in Japanese PBC patients. Springer, 2011 PBC nationallicence SNPs nationallicence CTLA4 nationallicence SLC4A2 nationallicence Autoantibody nationallicence Aiba Yoshihiro Clinical Research Center, National Hospital Organization Nagasaki Medical Center, 2-1001-1 Kubara, 856-8562, Omura, Nagasaki, Japan aut Nakamura Minoru Clinical Research Center, National Hospital Organization Nagasaki Medical Center, 2-1001-1 Kubara, 856-8562, Omura, Nagasaki, Japan aut Joshita Satoru Division of Gastroenterology and Hepatology, Department of Medicine, Shinshu University School of Medicine, Matsumoto, Japan aut Inamine Tatsuo Department of Pharmacotherapeutics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan aut Komori Atsumasa Clinical Research Center, National Hospital Organization Nagasaki Medical Center, 2-1001-1 Kubara, 856-8562, Omura, Nagasaki, Japan aut Yoshizawa Kaname Division of Gastroenterology and Hepatology, Department of Medicine, Shinshu University School of Medicine, Matsumoto, Japan aut Umemura Takeji Division of Gastroenterology and Hepatology, Department of Medicine, Shinshu University School of Medicine, Matsumoto, Japan aut Horie Hitomi Clinical Research Center, National Hospital Organization Nagasaki Medical Center, 2-1001-1 Kubara, 856-8562, Omura, Nagasaki, Japan aut Migita Kiyoshi Clinical Research Center, National Hospital Organization Nagasaki Medical Center, 2-1001-1 Kubara, 856-8562, Omura, Nagasaki, Japan aut Yatsuhashi Hiroshi Clinical Research Center, National Hospital Organization Nagasaki Medical Center, 2-1001-1 Kubara, 856-8562, Omura, Nagasaki, Japan aut Nakamuta Makoto Headquarters of PBC Study Group in National Hospital Organization Study Group for Liver Disease in Japan (NHOSLJ), Omura, Japan aut Fukushima Nobuyoshi Headquarters of PBC Study Group in National Hospital Organization Study Group for Liver Disease in Japan (NHOSLJ), Omura, Japan aut Saoshiro Takeo Headquarters of PBC Study Group in National Hospital Organization Study Group for Liver Disease in Japan (NHOSLJ), Omura, Japan aut Hayashi Shigeki Headquarters of PBC Study Group in National Hospital Organization Study Group for Liver Disease in Japan (NHOSLJ), Omura, Japan aut Kouno Hiroshi Headquarters of PBC Study Group in National Hospital Organization Study Group for Liver Disease in Japan (NHOSLJ), Omura, Japan aut Ota Hajime Headquarters of PBC Study Group in National Hospital Organization Study Group for Liver Disease in Japan (NHOSLJ), Omura, Japan aut Muro Toyokichi Headquarters of PBC Study Group in National Hospital Organization Study Group for Liver Disease in Japan (NHOSLJ), Omura, Japan aut Watanabe Yukio Headquarters of PBC Study Group in National Hospital Organization Study Group for Liver Disease in Japan (NHOSLJ), Omura, Japan aut Nakamura Yoko Headquarters of PBC Study Group in National Hospital Organization Study Group for Liver Disease in Japan (NHOSLJ), Omura, Japan aut Komeda Toshiki Headquarters of PBC Study Group in National Hospital Organization Study Group for Liver Disease in Japan (NHOSLJ), Omura, Japan aut Shimada Masaaki Headquarters of PBC Study Group in National Hospital Organization Study Group for Liver Disease in Japan (NHOSLJ), Omura, Japan aut Masaki Naohiko Headquarters of PBC Study Group in National Hospital Organization Study Group for Liver Disease in Japan (NHOSLJ), Omura, Japan aut Komatsu Tatsuji Headquarters of PBC Study Group in National Hospital Organization Study Group for Liver Disease in Japan (NHOSLJ), Omura, Japan aut Yagura Michiyasu Headquarters of PBC Study Group in National Hospital Organization Study Group for Liver Disease in Japan (NHOSLJ), Omura, Japan aut Sugi Kazuhiro Headquarters of PBC Study Group in National Hospital Organization Study Group for Liver Disease in Japan (NHOSLJ), Omura, Japan aut Koga Michiaki Headquarters of PBC Study Group in National Hospital Organization Study Group for Liver Disease in Japan (NHOSLJ), Omura, Japan aut Tsukamoto Kazuhiro Department of Pharmacotherapeutics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan aut Tanaka Eiji Division of Gastroenterology and Hepatology, Department of Medicine, Shinshu University School of Medicine, Matsumoto, Japan aut Ishibashi Hiromi Clinical Research Center, National Hospital Organization Nagasaki Medical Center, 2-1001-1 Kubara, 856-8562, Omura, Nagasaki, Japan aut Journal of Gastroenterology Springer Japan 46/10(2011-10-01), 1203-1212 0944-1174 46:10<1203 2011 46 535 https://doi.org/10.1007/s00535-011-0417-7 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00535-011-0417-7 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Aiba Yoshihiro Clinical Research Center, National Hospital Organization Nagasaki Medical Center, 2-1001-1 Kubara, 856-8562, Omura, Nagasaki, Japan aut NATIONALLICENCE 700 1- Nakamura Minoru Clinical Research Center, National Hospital Organization Nagasaki Medical Center, 2-1001-1 Kubara, 856-8562, Omura, Nagasaki, Japan aut NATIONALLICENCE 700 1- Joshita Satoru Division of Gastroenterology and Hepatology, Department of Medicine, Shinshu University School of Medicine, Matsumoto, Japan aut NATIONALLICENCE 700 1- Inamine Tatsuo Department of Pharmacotherapeutics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan aut NATIONALLICENCE 700 1- Komori Atsumasa Clinical Research Center, National Hospital Organization Nagasaki Medical Center, 2-1001-1 Kubara, 856-8562, Omura, Nagasaki, Japan aut NATIONALLICENCE 700 1- Yoshizawa Kaname Division of Gastroenterology and Hepatology, Department of Medicine, Shinshu University School of Medicine, Matsumoto, Japan aut NATIONALLICENCE 700 1- Umemura Takeji Division of Gastroenterology and Hepatology, Department of Medicine, Shinshu University School of Medicine, Matsumoto, Japan aut NATIONALLICENCE 700 1- Horie Hitomi Clinical Research Center, National Hospital Organization Nagasaki Medical Center, 2-1001-1 Kubara, 856-8562, Omura, Nagasaki, Japan aut NATIONALLICENCE 700 1- Migita Kiyoshi Clinical Research Center, National Hospital Organization Nagasaki Medical Center, 2-1001-1 Kubara, 856-8562, Omura, Nagasaki, Japan aut NATIONALLICENCE 700 1- Yatsuhashi Hiroshi Clinical Research Center, National Hospital Organization Nagasaki Medical Center, 2-1001-1 Kubara, 856-8562, Omura, Nagasaki, Japan aut NATIONALLICENCE 700 1- Nakamuta Makoto Headquarters of PBC Study Group in National Hospital Organization Study Group for Liver Disease in Japan (NHOSLJ), Omura, Japan aut NATIONALLICENCE 700 1- Fukushima Nobuyoshi Headquarters of PBC Study Group in National Hospital Organization Study Group for Liver Disease in Japan (NHOSLJ), Omura, Japan aut NATIONALLICENCE 700 1- Saoshiro Takeo Headquarters of PBC Study Group in National Hospital Organization Study Group for Liver Disease in Japan (NHOSLJ), Omura, Japan aut NATIONALLICENCE 700 1- Hayashi Shigeki Headquarters of PBC Study Group in National Hospital Organization Study Group for Liver Disease in Japan (NHOSLJ), Omura, Japan aut NATIONALLICENCE 700 1- Kouno Hiroshi Headquarters of PBC Study Group in National Hospital Organization Study Group for Liver Disease in Japan (NHOSLJ), Omura, Japan aut NATIONALLICENCE 700 1- Ota Hajime Headquarters of PBC Study Group in National Hospital Organization Study Group for Liver Disease in Japan (NHOSLJ), Omura, Japan aut NATIONALLICENCE 700 1- Muro Toyokichi Headquarters of PBC Study Group in National Hospital Organization Study Group for Liver Disease in Japan (NHOSLJ), Omura, Japan aut NATIONALLICENCE 700 1- Watanabe Yukio Headquarters of PBC Study Group in National Hospital Organization Study Group for Liver Disease in Japan (NHOSLJ), Omura, Japan aut NATIONALLICENCE 700 1- Nakamura Yoko Headquarters of PBC Study Group in National Hospital Organization Study Group for Liver Disease in Japan (NHOSLJ), Omura, Japan aut NATIONALLICENCE 700 1- Komeda Toshiki Headquarters of PBC Study Group in National Hospital Organization Study Group for Liver Disease in Japan (NHOSLJ), Omura, Japan aut NATIONALLICENCE 700 1- Shimada Masaaki Headquarters of PBC Study Group in National Hospital Organization Study Group for Liver Disease in Japan (NHOSLJ), Omura, Japan aut NATIONALLICENCE 700 1- Masaki Naohiko Headquarters of PBC Study Group in National Hospital Organization Study Group for Liver Disease in Japan (NHOSLJ), Omura, Japan aut NATIONALLICENCE 700 1- Komatsu Tatsuji Headquarters of PBC Study Group in National Hospital Organization Study Group for Liver Disease in Japan (NHOSLJ), Omura, Japan aut NATIONALLICENCE 700 1- Yagura Michiyasu Headquarters of PBC Study Group in National Hospital Organization Study Group for Liver Disease in Japan (NHOSLJ), Omura, Japan aut NATIONALLICENCE 700 1- Sugi Kazuhiro Headquarters of PBC Study Group in National Hospital Organization Study Group for Liver Disease in Japan (NHOSLJ), Omura, Japan aut NATIONALLICENCE 700 1- Koga Michiaki Headquarters of PBC Study Group in National Hospital Organization Study Group for Liver Disease in Japan (NHOSLJ), Omura, Japan aut NATIONALLICENCE 700 1- Tsukamoto Kazuhiro Department of Pharmacotherapeutics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan aut NATIONALLICENCE 700 1- Tanaka Eiji Division of Gastroenterology and Hepatology, Department of Medicine, Shinshu University School of Medicine, Matsumoto, Japan aut NATIONALLICENCE 700 1- Ishibashi Hiromi Clinical Research Center, National Hospital Organization Nagasaki Medical Center, 2-1001-1 Kubara, 856-8562, Omura, Nagasaki, Japan aut NATIONALLICENCE 773 0- Journal of Gastroenterology Springer Japan 46/10(2011-10-01), 1203-1212 0944-1174 46:10<1203 2011 46 535 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer