Systemic sclerosis (SSc) is a rare autoimmune disease with high mortality, characterized by chronic inflammation and fibrosis, which are processes associated with higher serum tumor necrosis factor-α (sTNF-α) levels. TNFA -308G>A and -238G>A polymorphisms have been associated with higher sTNF-α levels. In this study, we genotyped the TNFA -308G>A and -238G>A polymorphisms in 53 SSc patients and 115 unrelated control subjects (CS) from southern Mexico. The TNFA mRNA expression and sTNF-α levels were also quantified by qPCR and enzyme-linked immunosorbent assays, respectively. TNFA -308GA genotype was associated with disease susceptibility according to a codominant genetic model (OR = 3.2, 95% CI 1.05-9.75, p = 0.03), and with higher anti-fibrillarin antibodies (p = 0.01), and higher skin thickening (p = 0.006). TNFA -238GA was not associated with SSc risk. TNFA mRNA expression and sTNF-α levels were similar between SSc patients and CS and were not statistically associated with the TNFA polymorphisms; however, a correlation (rho = 0.362, p = 0.009) between sTNF-α levels with anti-RNA polymerase III antibodies was observed in the SSc patients. In conclusion, the -308G>A polymorphism is a genetic marker of SSc susceptibility in population from southern Mexico, and it is associated with skin thickening and anti-fibrillarin antibodies. In addition, sTNF-α levels correlate positively with the anti-RNA pol III antibodies levels.
Keywords: Autoantibodies; Systemic sclerosis; TNF-α; TNFA gene polymorphisms; TNFA mRNA expression.