Association of STAT4 with susceptibility to rheumatoid arthritis and systemic lupus erythematosus in the Japanese population

Shu Kobayashi, Katsunori Ikari, Hirotaka Kaneko, Yuta Kochi, Kazuhiko Yamamoto, Kenichi Shimane, Yusuke Nakamura, Yoshiaki Toyama, Takeshi Mochizuki, So Tsukahara, Yasushi Kawaguchi, Chihiro Terai, Masako Hara, Taisuke Tomatsu, Hisashi Yamanaka, Takahiko Horiuchi, Kayoko Tao, Koji Yasutomo, Daisuke Hamada, Natsuo YasuiHiroshi Inoue, Mitsuo Itakura, Hiroshi Okamoto, Naoyuki Kamatani, Shigeki Momohara

Research output: Contribution to journalArticlepeer-review

133 Citations (Scopus)


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 × 10-9) and 1.61 (P = 2.1 × 10-11) for allele frequency distribution; these ORs were quite similar to those previously observed in the Caucasian population. Conclusion. 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.

Original languageEnglish
Pages (from-to)1940-1946
Number of pages7
JournalArthritis and Rheumatism
Issue number7
Publication statusPublished - 2008 Jul
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)


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