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Multiple sclerosis (MS) has been associated with low levels of 25-hydroxyvitamin D (25(OH)D). Several genetic polymorphisms of the vitamin D receptor gene (VDRG), of whom Fok-I (rs10735810) has functional consequences for receptor protein structure and the immune system, have been studied in relation to MS with variable results. The purpose of our study was to assess an association of the Fok-I VDRG polymorphism with MS, and to further unravel the interaction of this polymorphism with vitamin D metabolism. Therefore, we genotyped 212 MS patients and 289 healthy controls for the Fok-I polymorphism and determined levels of the vitamin D metabolites 25(OH)D and 1,25(OH)₂D. No association of the Fok-I VDRG polymorphism with MS was found. The F-allele was associated with lower winter and summer serum 25(OH)D levels in our MS patients, and with lower 25(OH)D levels in healthy controls …