Association of osteopontin regulatory polymorphisms with systemic sclerosis

To test the involvement of osteopontin gene (OPN) in systemic sclerosis (SSc) susceptibility, two OPN single nucleotide polymorphisms previously reported to be associated with systemic lupus erythematosus, namely −156G/GG (proximal promoter) and +1239A/C (3′ untranslated region (UTR)), were tested in 357 Italian patients and 864 matched control subjects. OPN serum levels were determined by enzyme-linked immunosorbent assay in 32 patients and 116 controls. Compared with the controls, in SSc patients there was a significantly increased frequency of the alleles −156G (p = 0.0086), and +1239C (p = 0.00064), paralleling the association reported for systemic lupus erythematosus. According to logistic regression analysis, this association is primarily due to the effect of +1239 single nucleotide polymorphism. OPN serum levels were significantly higher in SSc patients than in controls (p = 0.00025). These data suggest that OPN genetic variations have a role in SSc susceptibility, reporting for the first time an involvement of this molecule in SSc pathogenesis and emphasizing that SSc shares pathogenetic mechanisms with other autoimmune diseases.