title: Association of STAT4 polymorphisms with susceptibility to type-1 autoimmune hepatitis in the Japanese population.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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
  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.
authors.affiliation: NHO-AIH Study Group, Nagasaki Medical Center, Omura, Nagasaki, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Migita
authors.forename: Minoru
authors.initials: M
authors.lastname: Nakamura
authors.forename: Seigo
authors.initials: S
authors.lastname: Abiru
authors.forename: Yuka
authors.initials: Y
authors.lastname: Jiuchi
authors.forename: Shinya
authors.initials: S
authors.lastname: Nagaoka
authors.forename: Atsumasa
authors.initials: A
authors.lastname: Komori
authors.forename: Satoru
authors.initials: S
authors.lastname: Hashimoto
authors.forename: Shigemune
authors.initials: S
authors.lastname: Bekki
authors.forename: Kazumi
authors.initials: K
authors.lastname: Yamasaki
authors.forename: Tatsuji
authors.initials: T
authors.lastname: Komatsu
authors.forename: Masaaki
authors.initials: M
authors.lastname: Shimada
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kouno
authors.forename: Taizo
authors.initials: T
authors.lastname: Hijioka
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Kohjima
authors.forename: Makoto
authors.initials: M
authors.lastname: Nakamuta
authors.forename: Michio
authors.initials: M
authors.lastname: Kato
authors.forename: Kaname
authors.initials: K
authors.lastname: Yoshizawa
authors.forename: Hajime
authors.initials: H
authors.lastname: Ohta
authors.forename: Yoko
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Eiichi
authors.initials: E
authors.lastname: Takezaki
authors.forename: Hideo
authors.initials: H
authors.lastname: Nishimura
authors.forename: Takeaki
authors.initials: T
authors.lastname: Sato
authors.forename: Keisuke
authors.initials: K
authors.lastname: Ario
authors.forename: Noboru
authors.initials: N
authors.lastname: Hirashima
authors.forename: Yukio
authors.initials: Y
authors.lastname: Oohara
authors.forename: Atsushi
authors.initials: A
authors.lastname: Naganuma
authors.forename: Toyokichi
authors.initials: T
authors.lastname: Muro
authors.forename: Hironori
authors.initials: H
authors.lastname: Sakai
authors.forename: Eiji
authors.initials: E
authors.lastname: Mita
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Sugi
authors.forename: Haruhiro
authors.initials: H
authors.lastname: Yamashita
authors.forename: Fujio
authors.initials: F
authors.lastname: Makita
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yatsuhashi
authors.forename: Hiromi
authors.initials: H
authors.lastname: Ishibashi
authors.forename: Michio
authors.initials: M
authors.lastname: Yasunami
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D044466:Asian People / Q000235:genetics; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D019693:Hepatitis, Autoimmune / Q000235:genetics*; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D050797:STAT4 Transcription Factor / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D050797:STAT4 Transcription Factor; C494090:STAT4 protein, human