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

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

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 languageEnglish
Article numbere71382
JournalPloS one
Volume8
Issue number8
DOIs
Publication statusPublished - Aug 22 2013
Externally publishedYes

All Science Journal Classification (ASJC) codes

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

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