title: Polymorphisms in vitamin D metabolism related genes and risk of multiple sclerosis.
abstract: The extent to which potential genetic determinants of vitamin D levels may be related to multiple sclerosis (MS) risk has not been thoroughly explored. The objective of this study was to determine whether polymorphisms in VDR, CYP27B1, CYP24A1, CYP2R1 and DBP are associated with the risk of MS and whether these variants may modify associations between environmental or dietary vitamin D on MS risk. A nested case-control study was conducted in two, large cohorts of US nurses, including 214 MS cases and 428 age-matched controls. Conditional logistic regression models were used to calculate relative risks (RR) and 95% confidence intervals (CIs) and to assess the significance of gene-environment interactions. No associations were observed for any of the single-nucleotide polymorphisms (SNPs) in VDR, CYP27B1, CYP24A1, CYP2R1 or DBP (p > 0.05 for all). The authors did observe an interaction (p = 0.04) between dietary intake of vitamin D and the vitamin D receptor FokI polymorphism on MS risk. The protective effect of increasing vitamin D was evident only in individuals with the 'ff ' genotype (RR = 0.2, 95% CI: 0.06, 0.78; p = 0.02 for 400 IU/day increase). It was concluded that this does not support a role for the selected SNPs involved in vitamin D metabolism in the etiology of MS. The finding of a marginally significant gene-environment interaction requires replication in larger datasets, but suggests future genetic studies may benefit from considering relevant environmental context.
authors.affiliation: Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA. ksimon@hsph.harvard.edu
authors.forename: K Claire
authors.initials: KC
authors.lastname: Simon
authors.forename: Kassandra L
authors.initials: KL
authors.lastname: Munger
authors.lastname: Xing Yang
authors.forename: Alberto
authors.initials: A
authors.lastname: Ascherio
mesh_terms: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism; D000328:Adult; D016022:Case-Control Studies; D053493:Cholestanetriol 26-Monooxygenase / Q000235:genetics / Q000378:metabolism; D000072467:Cytochrome P450 Family 2; D004032:Diet; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000235:genetics* / Q000378:metabolism; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism; D018570:Risk Assessment; D012307:Risk Factors; D013250:Steroid Hydroxylases / Q000235:genetics / Q000378:metabolism; D014481:United States; D014807:Vitamin D / Q000008:administration & dosage / Q000378:metabolism*; D014809:Vitamin D-Binding Protein / Q000235:genetics / Q000378:metabolism; D065668:Vitamin D3 24-Hydroxylase
chemical_list: D018167:Receptors, Calcitriol; D014809:Vitamin D-Binding Protein; D014807:Vitamin D; D013250:Steroid Hydroxylases; D000072467:Cytochrome P450 Family 2; C506833:CYP2R1 protein, human; D053493:Cholestanetriol 26-Monooxygenase; C585549:CYP24A1 protein, human; D065668:Vitamin D3 24-Hydroxylase; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase