Open AccessAssociation of STAT4 with susceptibility to rheumatoid arthritis and systemic lupus erythematosus in the Japanese population
Author(s) -
Kobayashi Shu,
Ikari Katsunori,
Kaneko Hirotaka,
Kochi Yuta,
Yamamoto Kazuhiko,
Shimane Kenichi,
Nakamura Yusuke,
Toyama Yoshiaki,
Mochizuki Takeshi,
Tsukahara So,
Kawaguchi Yasushi,
Terai Chihiro,
Hara Masako,
Tomatsu Taisuke,
Yamanaka Hisashi,
Horiuchi Takahiko,
Tao Kayoko,
Yasutomo Koji,
Hamada Daisuke,
Yasui Natsuo,
Inoue Hiroshi,
Itakura Mitsuo,
Okamoto Hiroshi,
Kamatani Naoyuki,
Momohara Shigeki
Publication year - 2008
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/art.23494
Subject(s) - stat4 , haplotype , single nucleotide polymorphism , immunology , medicine , rheumatoid arthritis , population , odds ratio , allele frequency , allele , genotype , genetics , biology , gene , stat3 , environmental health , stat
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 × 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.