Association study of TRAF1-C5 polymorphisms with susceptibility to rheumatoid arthritis and systemic lupus erythematosus in Japanese

K. Nishimoto, Y. Kochi, K. Ikari, K. Yamamoto, A. Suzuki, K. Shimane, Y. Nakamura, K. Yano, N. Iikuni, S. Tsukahara, N. Kamatani, H. Okamoto, H. Kaneko, Y. Kawaguchi, M. Hara, Y. Toyama, T. Horiuchi, K. Tao, D. Yasutomo, N. YasuiH. Inoue, M. Itakura, H. Yamanaka, S. Momohara

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Abstract

Objective: The primary aim of this study was to investigate the association of polymorphisms of TRAF1-C5, a newly identified rheumatoid arthritis (RA) risk locus in Caucasians, with susceptibility to RA and systemic lupus erythematosus (SLE) in Japanese populations. Gene expression levels of TRAF1 and C5 to assess the functional significance of genotypes were also analysed. Methods: A multicentre association study consisting of 4 RA case-control series (4397 cases and 2857 controls) and 3 SLE case-control series (591 cases and 2199 shared controls) was conducted. Genotyping was performed using TaqMan genotyping assay for two single nucleotide polymorphisms (SNPs) that showed the best evidence of association in the previous Caucasian studies. Quantifications of TRAF1 and C5 expression were performed with TaqMan expression assay. Results: Significant differences in allele frequency for both SNPs were observed between RA and control subjects (combined odds ratio =1.09), while no significant difference was detected between patients with SLE and controls. Interestingly, alleles rs3761847 A and rs10818488 G had increased the risk for RA in the present study, while they decreased the risk in the original studies. A significant difference was found between risk allele carriers and non-carriers of rs10818488 for the expression level of TRAF1 in phorbol myristate acetatestimulated lymphoblastoid cell lines (p=0.04). Conclusion: Association of TRAF1-C5 locus with RA susceptibility was detected in the Japanese populations with modest magnitude, while no significant association was observed for SLE. Significant positive effect of genotype on the expression of TRAF1 might support the genetic association between TRAF1 and RA.

Original languageEnglish
Pages (from-to)368-373
Number of pages6
JournalAnnals of the Rheumatic Diseases
Volume69
Issue number2
DOIs
Publication statusPublished - Feb 2010

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Biochemistry, Genetics and Molecular Biology(all)

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    Nishimoto, K., Kochi, Y., Ikari, K., Yamamoto, K., Suzuki, A., Shimane, K., Nakamura, Y., Yano, K., Iikuni, N., Tsukahara, S., Kamatani, N., Okamoto, H., Kaneko, H., Kawaguchi, Y., Hara, M., Toyama, Y., Horiuchi, T., Tao, K., Yasutomo, D., ... Momohara, S. (2010). Association study of TRAF1-C5 polymorphisms with susceptibility to rheumatoid arthritis and systemic lupus erythematosus in Japanese. Annals of the Rheumatic Diseases, 69(2), 368-373. https://doi.org/10.1136/ard.2008.104315