Background The tumor necrosis factor receptor-associated factor 1 (TRAF1) gene encodes TRAF1, which acts in association with TNF receptor family members and regulates cytokine signaling networks. Complement 5 (C5) is a pivotal member of the complement system. Product of TRAF1 and C5 is a potent chemo-attractant complement component and an essential effector of the TNF signaling cascade.
Objectives The aim of this study was to determine whether TRAF1-C5 polymorphisms confer susceptibility to rheumatoid arthritis (RA) in different populations.
Methods We conducted a meta-analysis of associations between the TRAF1-C5 rs10818488, rs3761847, rs2900180 and rs10760130 polymorphisms and RA susceptibility, using fixed and random effects models.
Results A total of 24 comparative studies were included in this meta-analysis, including 22,682 patients with RA and 23,493 controls. The meta-analysis showed an association between the second allele of rs10818488 and RA in all study subjects (OR 1.170, 95% CI 1.082-1.266, p = 8.2 x 10-6). Analysis after stratification by population indicated that the second allele of rs10818488 were associated with RA in Europeans, but not in Asians (OR 1.229, 95% CI 1.094-1.381, p = 0.001; OR 1.060, 95% CI 0.930-1.335, p = 0.092). The meta-analysis also indicated an association between the second allele of rs3761847 and RA in all study subjects (OR 1.098, 95% CI 1.019-1.184, p = 0.015). The second allele of rs3761847 was associated with RA in Europeans, but not in Asians (OR 1.156, 95% CI 1.006-1.327, p = 0.041; OR 1.049, 95% CI 0.952-1.156, p = 0.333). The meta-analysis revealed an association between the second allele of the rs2900180 polymorphism and the risk of developing RA in all study subjects and Europeans (OR 1.180, 95% CI 1.031-1.350, p = 0.016; OR 1.224, 95% CI 1.065-1.405, p = 0.004). An association between the second allele of rs10760130 and RA in Europeans (OR 1.072, 95% CI 1.002-1.147, p = 0.042) was also noted.
Conclusions This meta-analysis confirms that the TRAF1-C5 rs10818488, rs3761847, rs2900180 and rs10760130 polymorphisms are associated with RA susceptibility in Europeans. However, the TRAF1-C5 rs10818488 and rs3761847 polymorphisms are not associated with RA in Asians.
References Kurreeman FA, Goulielmos GN, Alizadeh BZ, Rueda B, Houwing-Duistermaat J, Sanchez E, Bevova M, Radstake TR, Vonk MC, Galanakis E, Ortego N, Verduyn W, Zervou MI, Roep BO, Dema B, Espino L, Urcelay E, Boumpas DT, van den Berg LH, Wijmenga C, Koeleman BP, Huizinga TW, Toes RE, Martin J (2010) The TRAF1-C5 region on chromosome 9q33 is associated with multiple autoimmune diseases. Ann Rheum Dis 69:696-699
Disclosure of Interest None Declared
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