Association of osteopontin regulatory polymorphisms with systemic sclerosis

Abstract

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.