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Osteopontin transcription is increased in the central nervous system of patients with multiple sclerosis and rats with experimental allergic encephalomyelitis; where expression correlates with disease severity. We typed four single nucleotide polymorphisms located in exons 6 and 7 of the osteopontin gene in a large cohort of 1056 multiple sclerosis patients and 325 controls. We did not find significant allelic differences of the screened polymorphisms between the cases and controls and there was no allelic association with disease severity. Despite strong theoretical reasons to consider osteopontin as a potential candidate, the results of our study argue against the gene being a susceptibility locus for either the development or clinical severity of MS.