Genome wide association studies have identified an association between SNPs in the 5' untranslated region of the TRAF1 gene with increased incidence and severity of rheumatoid arthritis and other rheumatic diseases.
Here we show that monocytes from healthy human subjects with a rheumatoid arthritis-associated single-nucleotide polymorphism (SNP) in the TRAF1 gene express less TRAF1 protein but greater amounts of inflammatory cytokines in response to lipopolysaccharide (LPS).
A real data application to detect the association between gene TRAF1-C5 and rheumatoid arthritis further shows good performance of the proposed procedure.
The minor allele for RA susceptibility, rs3761847 SNP in TRAF1/C5 region, was associated with a poor response in linear and logistic univariate and multivariate regression analyses.
Meta-analysis showed a weak association between TRAF1/C5 rs10818488 polymorphism and RA in all subjects (OR = 1.13, 95 % CI = 1.01–1.27, P heterogeneity < 0.001).
This meta-analysis confirms that the TRAF1-C5 rs10818488, rs3761847, rs2900180 and rs10760130 polymorphisms are associated with RA susceptibility in Europeans.
Taken together, our study demonstrates that the TRAF1/C5 polymorphism (rs10818488) may confer susceptibility to RA in North Africa population, and in European population, it might be a contributory factor towards SLE.
Sixty-three RA patients were included.Nine genes (13 SNPs) were subsequently analyzed, including those coding for cytokines involved in synovitis (IL10, LTA, TGFβ1, TNF-α, TNF receptor II) and genes associated with RA susceptibility (-C5 TRAF1, STAT4, TNFAIP3 and PTPN22).
Our results are in keeping with a previous report and suggest that the TRAF1/C5 region is associated with risk of development of radiological erosions in IP/RA patients.
We first demonstrated that genetic variants at the TRAF1/C5 locus are significantly associated with RA in Han Chinese, suggesting that TRAF1/C5 may play a role in the development of RA in this population, which expands the pathogenesis role of TRAF1/C5 in a different ethnicity.
We also demonstrate that in the presence of SE, the minor allele of MMEL1-TNFRSF14 significantly reduces RA risk in a dominant manner, whereas TRAF1-C5 increases the risk.
In particular, recent discoveries highlight the importance of the CD40/NF-kappaB signaling pathway in RA, based on genetic association with several genes relevant to this pathway, including CD40, TRAF1, TNFAIP3, and REL.
A novel association with a 100-kb region on chromosome 9 that contains the tumor necrosis factor receptor-associated factor 1 (TRAF1) and C5 genes has been observed in some autoimmune rheumatic diseases, in particular in rheumatoid arthritis.