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Association study of TRAF1-C5 polymorphisms with susceptibility to rheumatoid arthritis and systemic lupus erythematosus in Japanese
  1. Kazumasa Nishimoto (kz-nishi{at}fc5.so-net.ne.jp)
  1. Tokyo Women's Medical University, Japan
    1. Yuta Kochi (ykochi{at}src.riken.jp)
    1. RIKEN, Japan
      1. Katsunori Ikari (kikari{at}mac.com)
      1. Tokyo Women's Medical University, Japan
        1. Kazuhiko Yamamoto (yamamoto-tky{at}umin.ac.jp)
        1. University of Tokyo, Japan
          1. Akari Suzuki (akaris{at}src.riken.jp)
          1. RIKEN, Japan
            1. Kenichi Shimane (kshimane{at}src.riken.jp)
            1. RIKEN, Japan
              1. Yusuke Nakamura (yusuke{at}ims.u-tokyo.ac.jp)
              1. University of Tokyo, Japan
                1. Koichiro Yano (kohchi{at}fd5.so-net.ne.jp)
                1. Tokyo Women's Medical University, Japan
                  1. Noriko Iikuni (iikuni{at}ior.twmu.ac.jp)
                  1. Tokyo Women's Medical University, Japan
                    1. So Tsukahara (stsuka{at}ior.twmu.ac.jp)
                    1. Tokyo Women's Medical University, Japan
                      1. Naoyuki Kamatani (kamatani{at}msb.biglobe.ne.jp)
                      1. Tokyo Women's Medical University, Japan
                        1. Hiroshi Okamoto (hokamoto{at}parkcity.ne.jp)
                        1. Tokyo Women's Medical University, Japan
                          1. Hirotaka Kaneko (hikaneko{at}ior.twmu.ac.jp)
                          1. Tokyo Women's Medical University, Japan
                            1. Yasushi Kawaguchi (y-kawa{at}ior.twmu.ac.jp)
                            1. Tokyo Women's Medical University, Japan
                              1. Masako Hara (mhara{at}ior.twmu.ac.jp)
                              1. Tokyo Women's Medical University, Japan
                                1. Yoshiaki Toyama (toyama{at}sc.itc.keio.ac.jp)
                                1. Keio University, Japan
                                  1. Takahiko Horiuchi (horiuchi{at}intmed1.med.kyushu-u.ac.jp)
                                  1. Kyushu University, Japan
                                    1. Kayoko Tao (kayokotao{at}basic.med.tokushima-u.ac.jp)
                                    1. Tokushima University, Japan
                                      1. Koji Yasumoto (yasutomo{at}basic.med.tokushima-u.ac.jp)
                                      1. Kyushu University, Japan
                                        1. Daisuke Hamada (hamaj{at}clin.med.tokushima-u.ac.jp)
                                        1. Tokushima University, Japan
                                          1. Natsuo Yasui (nyasui{at}clin.med.tokushima-u.ac.jp)
                                          1. Tokushima University, Japan
                                            1. Hiroshi Inoue (hinoue{at}genome.tokushima-u.ac.jp)
                                            1. Tokushima University, Japan
                                              1. Mitsuo Itakura (itakura{at}genome.tokushima-u.ac.jp)
                                              1. Tokushima University, Japan
                                                1. Hisashi Yamanaka (yamanaka{at}ior.twmu.ac.jp)
                                                1. Tokyo Women's Medical University, Japan
                                                  1. Shigeki Momohara (smomohara{at}ior.twmu.ac.jp)
                                                  1. Tokyo Women's Medical University, Japan

                                                    Abstract

                                                    Objective: One of the aims of this study was to investigate the association of polymorphisms of TRAF1-C5, a newly identified rheumatoid arthritis (RA)-risk locus in Caucasian, 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 analyzed.

                                                    Methods: We conducted a multi-center association study consisting of four RA case-control series (4397 cases and 2857 controls) and three SLE case-control series (591 cases and 2199 shared controls). Genotyping was performed using TaqMan genotyping assay for two 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 SLE patients and controls. Interestingly, alleles rs3761847 A and rs10818488 G had increased the risk for RA in our study, while they decreased the risk in the original studies. We found significant difference between the risk-allele carrier and non-carrier of rs10818488 for the expression level of TRAF1 in phorbol myristate acetate-stimulated lymophoblastoid 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.

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