title: Association of STAT4 with susceptibility to rheumatoid arthritis and systemic lupus erythematosus in the Japanese population.
abstract: OBJECTIVE
  STAT4 encodes a transcriptional factor that transmits signals induced by several key cytokines, and it might be a key molecule in the development of autoimmune diseases. Recently, a STAT4 haplotype was reported to be associated with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) in Caucasian populations. This was replicated in a Korean RA population. Interestingly, the degree of risk of RA susceptibility with the STAT4 haplotype was similar in the Caucasian and Korean populations. The present study was undertaken to investigate the effect of STAT4 on susceptibility to RA and SLE in the Japanese.
  
  
  METHODS
  We performed an association study using 3 independent Japanese RA case-control populations (total 3,567 cases and 2,199 controls) and 3 independent Japanese SLE populations (total 591 cases). All samples were genotyped using the TaqMan fluorogenic 5' nuclease assay for single-nucleotide polymorphism (SNP) rs7574865, which tags the susceptibility haplotype. The association of the SNP with disease susceptibility in each case-control study was calculated using Fisher's exact test, and the results were combined, using the Mantel-Haenszel method, to obtain combined odds ratios (ORs).
  
  
  RESULTS
  We observed a significant association of the STAT4 polymorphism with susceptibility to both RA and SLE. The combined ORs for RA and SLE, respectively, were 1.27 (P = 8.4 x 10(-9)) and 1.61 (P = 2.1 x 10(-11)) for allele frequency distribution; these ORs were quite similar to those previously observed in the Caucasian population.
  
  
  CONCLUSIONS
  We conclude that STAT4 is associated with RA and SLE in the Japanese. Our results indicate that STAT4 is a common genetic risk factor for autoimmune diseases, with similar strength across major racial groups.
authors.affiliation: Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Shu
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Katsunori
authors.initials: K
authors.lastname: Ikari
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Kaneko
authors.forename: Yuta
authors.initials: Y
authors.lastname: Kochi
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Kenichi
authors.initials: K
authors.lastname: Shimane
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Toyama
authors.forename: Takeshi
authors.initials: T
authors.lastname: Mochizuki
authors.forename: So
authors.initials: S
authors.lastname: Tsukahara
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kawaguchi
authors.forename: Chihiro
authors.initials: C
authors.lastname: Terai
authors.forename: Masako
authors.initials: M
authors.lastname: Hara
authors.forename: Taisuke
authors.initials: T
authors.lastname: Tomatsu
authors.forename: Hisashi
authors.initials: H
authors.lastname: Yamanaka
authors.forename: Takahiko
authors.initials: T
authors.lastname: Horiuchi
authors.forename: Kayoko
authors.initials: K
authors.lastname: Tao
authors.forename: Koji
authors.initials: K
authors.lastname: Yasutomo
authors.forename: Daisuke
authors.initials: D
authors.lastname: Hamada
authors.forename: Natsuo
authors.initials: N
authors.lastname: Yasui
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Inoue
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Itakura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Okamoto
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Kamatani
authors.forename: Shigeki
authors.initials: S
authors.lastname: Momohara
mesh_terms: D000368:Aged; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007564:Japan; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D050797:STAT4 Transcription Factor / Q000096:biosynthesis*
chemical_list: D050797:STAT4 Transcription Factor; C494090:STAT4 protein, human