Association of STAT4 Polymorphisms with Susceptibility to Type-1 Autoimmune Hepatitis in the Japanese Population

Kiyoshi Migita; Minoru Nakamura; Seigo Abiru; Yuka Jiuchi; Shinya Nagaoka; Atsumasa Komori; Satoru Hashimoto; Shigemune Bekki; Kazumi Yamasaki; Tatsuji Komatsu; Masaaki Shimada; Hiroshi Kouno; Taizo Hijioka; Motoyuki Kohjima; Makoto Nakamuta; Michio Kato; Kaname Yoshizawa; Hajime Ohta; Yoko Nakamura; Eiichi Takezaki; Hideo Nishimura; Takeaki Sato; Keisuke Ario; Noboru Hirashima; Yukio Oohara; Atsushi Naganuma; Toyokichi Muro; Hironori Sakai; Eiji Mita; Kazuhiro Sugi; Haruhiro Yamashita; Fujio Makita; Hiroshi Yatsuhashi; Hiromi Ishibashi; Michio Yasunami

doi:10.1371/journal.pone.0071382

Association of STAT4 Polymorphisms with Susceptibility to Type-1 Autoimmune Hepatitis in the Japanese Population

Kiyoshi Migita, Minoru Nakamura, Seigo Abiru, Yuka Jiuchi, Shinya Nagaoka, Atsumasa Komori, Satoru Hashimoto, Shigemune Bekki, Kazumi Yamasaki, Tatsuji Komatsu, Masaaki Shimada, Hiroshi Kouno, Taizo Hijioka, Motoyuki Kohjima, Makoto Nakamuta, Michio Kato, Kaname Yoshizawa, Hajime Ohta, Yoko Nakamura, Eiichi TakezakiHideo Nishimura, Takeaki Sato, Keisuke Ario, Noboru Hirashima, Yukio Oohara, Atsushi Naganuma, Toyokichi Muro, Hironori Sakai, Eiji Mita, Kazuhiro Sugi, Haruhiro Yamashita, Fujio Makita, Hiroshi Yatsuhashi, Hiromi Ishibashi, Michio Yasunami

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Abstract

Background/Aims:Recent studies demonstrated an association of STAT4 polymorphisms with autoimmune diseases including systemic lupus erythematosus and rheumatoid arthritis, indicating multiple autoimmune diseases share common susceptibility genes. We therefore investigated the influence of STAT4 polymorphisms on the susceptibility and phenotype of type-1 autoimmune hepatitis in a Japanese National Hospital Organization (NHO) AIH multicenter cohort study.Methodology/Principal Findings:Genomic DNA from 460 individuals of Japanese origin including 230 patients with type-1 autoimmune hepatitis and 230 healthy controls was analyzed for two single nucleotide polymorphisms in the STAT4 gene (rs7574865, rs7582694). The STAT4 rs7574865T allele conferred risk for type-1 autoimmune hepatitis (OR = 1.61, 95% CI = 1.23-2.11; P = 0.001), and patients without accompanying autoimmune diseases exhibited an association with the rs7574865T allele (OR = 1.50, 95%CI = 1.13-1.99; P = 0.005). Detailed genotype-phenotype analysis of type-1 autoimmune hepatitis patients with (n = 44) or without liver cirrhosis (n = 186) demonstrated that rs7574865 was not associated with the development of liver cirrhosis and phenotype (biochemical data and the presence of auto-antibodies).Conclusions/Significance:This is the first study to show a positive association between a STAT4 polymorphism and type-1 autoimmune hepatitis, suggesting that autoimmune hepatitis shares a gene commonly associated with risk for other autoimmune diseases.

Original language	English
Article number	e71382
Journal	PloS one
Volume	8
Issue number	8
DOIs	https://doi.org/10.1371/journal.pone.0071382
Publication status	Published - Aug 22 2013
Externally published	Yes

All Science Journal Classification (ASJC) codes

Biochemistry, Genetics and Molecular Biology(all)
Agricultural and Biological Sciences(all)
General

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1371/journal.pone.0071382

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Migita, K., Nakamura, M., Abiru, S., Jiuchi, Y., Nagaoka, S., Komori, A., Hashimoto, S., Bekki, S., Yamasaki, K., Komatsu, T., Shimada, M., Kouno, H., Hijioka, T., Kohjima, M., Nakamuta, M., Kato, M., Yoshizawa, K., Ohta, H., Nakamura, Y., ... Yasunami, M. (2013). Association of STAT4 Polymorphisms with Susceptibility to Type-1 Autoimmune Hepatitis in the Japanese Population. PloS one, 8(8), [e71382]. https://doi.org/10.1371/journal.pone.0071382

Migita, K, Nakamura, M, Abiru, S, Jiuchi, Y, Nagaoka, S, Komori, A, Hashimoto, S, Bekki, S, Yamasaki, K, Komatsu, T, Shimada, M, Kouno, H, Hijioka, T, Kohjima, M, Nakamuta, M, Kato, M, Yoshizawa, K, Ohta, H, Nakamura, Y, Takezaki, E, Nishimura, H, Sato, T, Ario, K, Hirashima, N, Oohara, Y, Naganuma, A, Muro, T, Sakai, H, Mita, E, Sugi, K, Yamashita, H, Makita, F, Yatsuhashi, H, Ishibashi, H & Yasunami, M 2013, 'Association of STAT4 Polymorphisms with Susceptibility to Type-1 Autoimmune Hepatitis in the Japanese Population', PloS one, vol. 8, no. 8, e71382. https://doi.org/10.1371/journal.pone.0071382

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title = "Association of STAT4 Polymorphisms with Susceptibility to Type-1 Autoimmune Hepatitis in the Japanese Population",

abstract = "Background/Aims:Recent studies demonstrated an association of STAT4 polymorphisms with autoimmune diseases including systemic lupus erythematosus and rheumatoid arthritis, indicating multiple autoimmune diseases share common susceptibility genes. We therefore investigated the influence of STAT4 polymorphisms on the susceptibility and phenotype of type-1 autoimmune hepatitis in a Japanese National Hospital Organization (NHO) AIH multicenter cohort study.Methodology/Principal Findings:Genomic DNA from 460 individuals of Japanese origin including 230 patients with type-1 autoimmune hepatitis and 230 healthy controls was analyzed for two single nucleotide polymorphisms in the STAT4 gene (rs7574865, rs7582694). The STAT4 rs7574865T allele conferred risk for type-1 autoimmune hepatitis (OR = 1.61, 95% CI = 1.23-2.11; P = 0.001), and patients without accompanying autoimmune diseases exhibited an association with the rs7574865T allele (OR = 1.50, 95%CI = 1.13-1.99; P = 0.005). Detailed genotype-phenotype analysis of type-1 autoimmune hepatitis patients with (n = 44) or without liver cirrhosis (n = 186) demonstrated that rs7574865 was not associated with the development of liver cirrhosis and phenotype (biochemical data and the presence of auto-antibodies).Conclusions/Significance:This is the first study to show a positive association between a STAT4 polymorphism and type-1 autoimmune hepatitis, suggesting that autoimmune hepatitis shares a gene commonly associated with risk for other autoimmune diseases.",

author = "Kiyoshi Migita and Minoru Nakamura and Seigo Abiru and Yuka Jiuchi and Shinya Nagaoka and Atsumasa Komori and Satoru Hashimoto and Shigemune Bekki and Kazumi Yamasaki and Tatsuji Komatsu and Masaaki Shimada and Hiroshi Kouno and Taizo Hijioka and Motoyuki Kohjima and Makoto Nakamuta and Michio Kato and Kaname Yoshizawa and Hajime Ohta and Yoko Nakamura and Eiichi Takezaki and Hideo Nishimura and Takeaki Sato and Keisuke Ario and Noboru Hirashima and Yukio Oohara and Atsushi Naganuma and Toyokichi Muro and Hironori Sakai and Eiji Mita and Kazuhiro Sugi and Haruhiro Yamashita and Fujio Makita and Hiroshi Yatsuhashi and Hiromi Ishibashi and Michio Yasunami",

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doi = "10.1371/journal.pone.0071382",

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T1 - Association of STAT4 Polymorphisms with Susceptibility to Type-1 Autoimmune Hepatitis in the Japanese Population

AU - Migita, Kiyoshi

AU - Nakamura, Minoru

AU - Abiru, Seigo

AU - Jiuchi, Yuka

AU - Nagaoka, Shinya

AU - Komori, Atsumasa

AU - Hashimoto, Satoru

AU - Bekki, Shigemune

AU - Yamasaki, Kazumi

AU - Komatsu, Tatsuji

AU - Shimada, Masaaki

AU - Kouno, Hiroshi

AU - Hijioka, Taizo

AU - Kohjima, Motoyuki

AU - Nakamuta, Makoto

AU - Kato, Michio

AU - Yoshizawa, Kaname

AU - Ohta, Hajime

AU - Nakamura, Yoko

AU - Takezaki, Eiichi

AU - Nishimura, Hideo

AU - Sato, Takeaki

AU - Ario, Keisuke

AU - Hirashima, Noboru

AU - Oohara, Yukio

AU - Naganuma, Atsushi

AU - Muro, Toyokichi

AU - Sakai, Hironori

AU - Mita, Eiji

AU - Sugi, Kazuhiro

AU - Yamashita, Haruhiro

AU - Makita, Fujio

AU - Yatsuhashi, Hiroshi

AU - Ishibashi, Hiromi

AU - Yasunami, Michio

PY - 2013/8/22

Y1 - 2013/8/22

N2 - Background/Aims:Recent studies demonstrated an association of STAT4 polymorphisms with autoimmune diseases including systemic lupus erythematosus and rheumatoid arthritis, indicating multiple autoimmune diseases share common susceptibility genes. We therefore investigated the influence of STAT4 polymorphisms on the susceptibility and phenotype of type-1 autoimmune hepatitis in a Japanese National Hospital Organization (NHO) AIH multicenter cohort study.Methodology/Principal Findings:Genomic DNA from 460 individuals of Japanese origin including 230 patients with type-1 autoimmune hepatitis and 230 healthy controls was analyzed for two single nucleotide polymorphisms in the STAT4 gene (rs7574865, rs7582694). The STAT4 rs7574865T allele conferred risk for type-1 autoimmune hepatitis (OR = 1.61, 95% CI = 1.23-2.11; P = 0.001), and patients without accompanying autoimmune diseases exhibited an association with the rs7574865T allele (OR = 1.50, 95%CI = 1.13-1.99; P = 0.005). Detailed genotype-phenotype analysis of type-1 autoimmune hepatitis patients with (n = 44) or without liver cirrhosis (n = 186) demonstrated that rs7574865 was not associated with the development of liver cirrhosis and phenotype (biochemical data and the presence of auto-antibodies).Conclusions/Significance:This is the first study to show a positive association between a STAT4 polymorphism and type-1 autoimmune hepatitis, suggesting that autoimmune hepatitis shares a gene commonly associated with risk for other autoimmune diseases.

AB - Background/Aims:Recent studies demonstrated an association of STAT4 polymorphisms with autoimmune diseases including systemic lupus erythematosus and rheumatoid arthritis, indicating multiple autoimmune diseases share common susceptibility genes. We therefore investigated the influence of STAT4 polymorphisms on the susceptibility and phenotype of type-1 autoimmune hepatitis in a Japanese National Hospital Organization (NHO) AIH multicenter cohort study.Methodology/Principal Findings:Genomic DNA from 460 individuals of Japanese origin including 230 patients with type-1 autoimmune hepatitis and 230 healthy controls was analyzed for two single nucleotide polymorphisms in the STAT4 gene (rs7574865, rs7582694). The STAT4 rs7574865T allele conferred risk for type-1 autoimmune hepatitis (OR = 1.61, 95% CI = 1.23-2.11; P = 0.001), and patients without accompanying autoimmune diseases exhibited an association with the rs7574865T allele (OR = 1.50, 95%CI = 1.13-1.99; P = 0.005). Detailed genotype-phenotype analysis of type-1 autoimmune hepatitis patients with (n = 44) or without liver cirrhosis (n = 186) demonstrated that rs7574865 was not associated with the development of liver cirrhosis and phenotype (biochemical data and the presence of auto-antibodies).Conclusions/Significance:This is the first study to show a positive association between a STAT4 polymorphism and type-1 autoimmune hepatitis, suggesting that autoimmune hepatitis shares a gene commonly associated with risk for other autoimmune diseases.

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Association of STAT4 Polymorphisms with Susceptibility to Type-1 Autoimmune Hepatitis in the Japanese Population

Abstract

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