RESEARCH - Association study of TRAF-1-C5 polymorphisms with susceptibility to RA and SLE

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Ann Rheum Dis. Published Online First: 30 March 2009.

doi:10.1136/ard.2008.104315

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Extended Report

Association study of TRAF1-C5 polymorphisms with susceptibility to

rheumatoid arthritis and systemic lupus erythematosus in Japanese

Kazumasa Nishimoto 1, Yuta Kochi 2, Katsunori Ikari 1*, Kazuhiko

Yamamoto 3, Akari Suzuki 2, Kenichi Shimane 2, Yusuke Nakamura 3,

Koichiro Yano 1, Noriko Iikuni 1, So Tsukahara 1, Naoyuki Kamatani 1,

Hiroshi Okamoto 1, Hirotaka Kaneko 1, Yasushi Kawaguchi 1, Masako Hara

1, Yoshiaki Toyama 4, Takahiko Horiuchi 5, Kayoko Tao 6, Koji Yasumoto

5, Daisuke Hamada 6, Natsuo Yasui 6, Hiroshi Inoue 6, Mitsuo Itakura

6, Hisashi Yamanaka 1 and Shigeki Momohara 1

1 Tokyo Women's Medical University, Japan

2 RIKEN, Japan

3 University of Tokyo, Japan

4 Keio University, Japan

5 Kyushu University, Japan

6 Tokushima 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.

http://ard.bmj.com/cgi/content/abstract/ard.2008.104315v1?papetoc

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