title: The vitamin D receptor gene is associated with Alzheimer's disease.
abstract: Vitamin D may have a role in brain function. Low levels have been frequently associated with cognitive decline and may contribute to diseases of the nervous system. The vitamin D receptor (VDR) is widely expressed in human brain. Vitamin D appears to be neuroprotective and may regulate inflammation in the brain. We examined two VDR polymorphisms, Apa1 and Taq1. We used DNA from 255 Alzheimer's disease (AD) cases and 260 cognitively screened elderly controls from the longitudinal cohort of the Oxford Project to Investigate Memory and Ageing (OPTIMA). The presence of each of the linked alleles, Apa1 T and Taq1 G, was associated with the risk of AD, particularly in people <75 years old: odds ratios ≥3.0 and p≤0.005. We also found preliminary evidence of interactions associated with AD between these polymorphisms and two other genes involved in the regulation of inflammation, interleukin-10 (IL10) and dopamine β-hydroxylase (DBH): synergy factors ≥3.4, uncorrected p<0.05. These associations are biologically plausible and are consistent with a role for vitamin D in AD. Nevertheless, we consider this to be a hypothesis-generating study, which needs to be replicated in a larger dataset.
authors.affiliation: Oxford Project to Investigate Memory and Ageing (OPTIMA), University Department of Pharmacology, Oxford OX1 3QT, UK. Electronic address: donald.lehmann@pharm.ox.ac.uk.
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Lehmann
authors.affiliation: Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Norway; University Department of Pharmacology, Oxford OX1 3QT, UK. Electronic address: Helga.Refsum@medisin.uio.no.
authors.forename: Helga
authors.initials: H
authors.lastname: Refsum
authors.affiliation: Oxford Project to Investigate Memory and Ageing (OPTIMA), University Department of Pharmacology, Oxford OX1 3QT, UK. Electronic address: donald.warden@pharm.ox.ac.uk.
authors.forename: Donald R
authors.initials: DR
authors.lastname: Warden
authors.affiliation: School of Molecular Medical Sciences, Institute of Genetics, University of Nottingham, Queens Medical Centre, Nottingham NG7 2UH, UK. Electronic address: mrxcm3@nottingham.ac.uk.
authors.forename: Christopher
authors.initials: C
authors.lastname: Medway
authors.affiliation: Nuffield Department of Medicine, University of Oxford, Level 4, John Radcliffe Hospital, Oxford OX3 9DU, UK. Electronic address: gordon.wilcock@ndm.ox.ac.uk.
authors.forename: Gordon K
authors.initials: GK
authors.lastname: Wilcock
authors.affiliation: Oxford Project to Investigate Memory and Ageing (OPTIMA), University Department of Pharmacology, Oxford OX1 3QT, UK. Electronic address: david.smith@pharm.ox.ac.uk.
authors.forename: A David
authors.initials: AD
authors.lastname: Smith
mesh_terms: D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics; D015331:Cohort Studies; D004247:DNA / Q000235:genetics; D004299:Dopamine beta-Hydroxylase / Q000235:genetics; D006801:Humans; D007249:Inflammation / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D018167:Receptors, Calcitriol / Q000235:genetics*; D012306:Risk
chemical_list: D001057:Apolipoproteins E; D018167:Receptors, Calcitriol; D016753:Interleukin-10; D004247:DNA; D004299:Dopamine beta-Hydroxylase