caa a22 4500 445808004 CHVBK 20180317145202.0 cr unu---uuuuu 170323e20110901xx s 000 0 eng 10.1007/s00415-011-6001-5 doi (NATIONALLICENCE)springer-10.1007/s00415-011-6001-5 Genetic predictors of 25-hydroxyvitamin D levels and risk of multiple sclerosis [Elektronische Daten] [Kelly Simon, K. Munger, P. Kraft, D. Hunter, P. De Jager, A. Ascherio] Risk of multiple sclerosis (MS) decreases with increasing plasma levels of 25-hydroxyvitamin D [25(OH)D]. If this association reflected a protective effect of vitamin D, MS risk should be lower among individuals carrying genetic variants that predict high 25(OH)D levels. The aim of the study was to determine whether individuals with genotypes predicting higher 25(OH)D levels have decreased MS risk. Logistic regression was used to assess the association between single nucleotide polymorphisms (SNPs) associated with 25(OH)D levels and MS risk in 1,655 cases and 6,349 controls. Analyses were further stratified by HLA-DR15 status, assessed by genotyping a single SNP strongly correlated with the HLA DRB1*1501 risk haplotype, and complemented by considering a SNP near CYP27B1. SNPs in GC were predictors of 25(OH)D levels, but not MS risk, in either HLA-DR15 negative or HLA-DR15 positive individuals. In contrast, there was a suggestion of a difference in the effect of a CYP2R1 allele dependent on HLA-DR15 genotype. The ‘A' allele of CYP2R1 rs10741657 was associated with increased 25(OH)D levels and a non-significant reduced MS risk among HLA-DR15 negative (OR=0.89, 95% CI: 0.79, 1.01) that was not apparent in HLA-DR15 positive individuals. The ‘C' allele of CYP27B1 rs703842 was inversely associated with MS risk; this association appeared stronger among HLA-DR15 negative (OR=0.79, 95% CI: 0.69, 0.90) compared to HLA-DR15 positive individuals (OR=0.91, 95% CI: 0.80, 1.04). This preliminary finding suggests the possibility that the putative beneficial effect of vitamin D on MS risk maybe attenuated in individuals carrying the HLA-DR15 MS risk allele. Springer-Verlag, 2011 Multiple sclerosis nationallicence Genetics nationallicence HLA-DR15 nationallicence Vitamin D nationallicence 25-hydroxyvitamin D nationallicence Simon Kelly Department of Nutrition, Harvard School of Public Health, 677 Huntington Ave, Building 2, 3rd floor, 02115, Boston, MA, USA aut Munger K. Department of Nutrition, Harvard School of Public Health, 677 Huntington Ave, Building 2, 3rd floor, 02115, Boston, MA, USA aut Kraft P. Program in Molecular and Genetic Epidemiology, Epidemiology Department, Harvard School of Public Health, Boston, MA, USA aut Hunter D. Program in Molecular and Genetic Epidemiology, Epidemiology Department, Harvard School of Public Health, Boston, MA, USA aut De Jager P. Program in Translational NeuroPsychiatric Genomics, Department of Neurology, Brigham and Women's Hospital, Boston, MA, USA aut Ascherio A. Department of Nutrition, Harvard School of Public Health, 677 Huntington Ave, Building 2, 3rd floor, 02115, Boston, MA, USA aut Journal of Neurology Springer-Verlag 258/9(2011-09-01), 1676-1682 0340-5354 258:9<1676 2011 258 415 https://doi.org/10.1007/s00415-011-6001-5 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00415-011-6001-5 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Simon Kelly Department of Nutrition, Harvard School of Public Health, 677 Huntington Ave, Building 2, 3rd floor, 02115, Boston, MA, USA aut NATIONALLICENCE 700 1- Munger K. Department of Nutrition, Harvard School of Public Health, 677 Huntington Ave, Building 2, 3rd floor, 02115, Boston, MA, USA aut NATIONALLICENCE 700 1- Kraft P. Program in Molecular and Genetic Epidemiology, Epidemiology Department, Harvard School of Public Health, Boston, MA, USA aut NATIONALLICENCE 700 1- Hunter D. Program in Molecular and Genetic Epidemiology, Epidemiology Department, Harvard School of Public Health, Boston, MA, USA aut NATIONALLICENCE 700 1- De Jager P. Program in Translational NeuroPsychiatric Genomics, Department of Neurology, Brigham and Women's Hospital, Boston, MA, USA aut NATIONALLICENCE 700 1- Ascherio A. Department of Nutrition, Harvard School of Public Health, 677 Huntington Ave, Building 2, 3rd floor, 02115, Boston, MA, USA aut NATIONALLICENCE 773 0- Journal of Neurology Springer-Verlag 258/9(2011-09-01), 1676-1682 0340-5354 258:9<1676 2011 258 415 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer