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).
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).
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.
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.