Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology characterized by cartilage and bone destruction. The main genetic determinant to RA, the shared epitope, maps to the HLA-DR locus, although this is not the only risk factor. The osteopontin (OPN) gene, with pleiotropic functions in inflammatory and immune responses, has been implicated in the pathogenesis of RA. We studied the association of polymorphisms in the OPN gene and predisposition to RA.
Analysis was performed in a case-control study with 263 patients and 478 controls. Four single nucleotide polymorphisms (SNP), 327T/C, 795C/T, 1128A/G, and 1284A/C, of the OPN gene were genotyped by primer-specific amplification in the presence of SYBR Green.
Distorted transmission of these polymorphisms was studied in 58 RA trios and 61 affected sibling pairs. These SNP demonstrated strong linkage disequilibrium. No statistically significant association was observed (80% power to exclude a genotypic relative risk of 1.49 at the 5% significance level, with minor allele frequencies of 28%). This lack of association with RA was found after stratification for the shared epitope as well.
Our data suggest that, unlike the reported effect of the OPN SNP conferring predisposition to common diseases such as multiple sclerosis or systemic lupus erythematosus, these OPN gene polymorphisms do not contribute to RA susceptibility in the Spanish population we studied.