Fok-I vitamin D receptor gene polymorphism (rs10735810) and vitamin D metabolism in multiple sclerosis

• Published in: Journal of neuroimmunology 2009-02, Vol.207 (1), p.117-121
• Main Authors: Smolders, Joost, Damoiseaux, Jan, Menheere, Paul, Tervaert, Jan Willem Cohen, Hupperts, Raymond
• Format: Article
• Language: English
• Subjects: 1,25-diydroxyvitamin D; 25-hydroxyvitamin D; Adult; Allergy and Immunology; Analysis of Variance; Calcitriol - blood; Chi-Square Distribution; Deoxyribonucleases, Type II Site-Specific - genetics; Disability Evaluation; Female; Gene Frequency; Genetic polymorphism; Genetic Predisposition to Disease; Genotype; Humans; Male; Middle Aged; Multiple sclerosis; Multiple Sclerosis - genetics; Multiple Sclerosis - metabolism; Neurology; Polymorphism, Genetic - genetics; Receptors, Calcitriol - genetics; Seasons; Vitamin D; Vitamin D - analogs & derivatives; Vitamin D - blood; Vitamin D - metabolism; Vitamin D receptor
• ISSN: 0165-5728; 1872-8421
• DOI: 10.1016/j.jneuroim.2008.12.011

Abstract 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)2 D. 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. Remarkably, the F-allele corresponded with higher 1,25(OH)2 D levels in MS patients. In all groups, carriers of the F-allele had higher 1,25(OH)2 D/ 25(OH)D-ratios compared to their f-allele counterparts. In conclusion, we demonstrated the importance of the Fok-I VDRG polymorphism for vitamin D metabolism. This should be taken into account in association and ultimately intervention studies on vitamin D and MS.