title: The multiple sclerosis susceptibility genes TAGAP and IL2RA are regulated by vitamin D in CD4+ T cells.
abstract: Multiple sclerosis (MS) is an inflammatory, demyelinating disorder of the central nervous system that develops in genetically susceptible individuals. The majority of the MS-associated gene variants are located in genetic regions with importance for T-cell differentiation. Vitamin D is a potent immunomodulator, and vitamin D deficiency has been suggested to be associated with increased MS disease susceptibility and activity. In CD4+ T cells, we have analyzed in vitro vitamin D responsiveness of genes that contain an MS-associated single-nucleotide polymorphism (SNP) and with one or more vitamin D response elements in their regulatory regions. We identify IL2RA and TAGAP as novel vitamin D target genes. The vitamin D response is observed in samples from both MS patients and controls, and is not dependent on the genotype of MS-associated SNPs in the respective genes.
authors.affiliation: Department of Neurology, Oslo University Hospital, Oslo, Norway.
authors.forename: T
authors.initials: T
authors.lastname: Berge
authors.affiliation: Department of Neurology, Oslo University Hospital, Oslo, Norway.|Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: I S
authors.initials: IS
authors.lastname: Leikfoss
authors.affiliation: Department of Neurology, Oslo University Hospital, Oslo, Norway.|Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: I S
authors.initials: IS
authors.lastname: Brorson
authors.affiliation: Department of Neurology, Oslo University Hospital, Oslo, Norway.|Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: S D
authors.initials: SD
authors.lastname: Bos
authors.affiliation: Department of Neurology, Oslo University Hospital, Oslo, Norway.|Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: C M
authors.initials: CM
authors.lastname: Page
authors.affiliation: Department of Neurology, Oslo University Hospital, Oslo, Norway.|Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: M W
authors.initials: MW
authors.lastname: Gustavsen
authors.affiliation: Department of Neurology, Oslo University Hospital, Oslo, Norway.|Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: A
authors.initials: A
authors.lastname: Bjølgerud
authors.affiliation: Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|Department of Neurology, Akershus University Hospital, Lørenskog, Norway.
authors.forename: T
authors.initials: T
authors.lastname: Holmøy
authors.affiliation: Department of Neurology, Oslo University Hospital, Oslo, Norway.
authors.forename: E G
authors.initials: EG
authors.lastname: Celius
authors.affiliation: Central Diagnostic Laboratory, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Damoiseaux
authors.affiliation: Department of Neurology, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Smolders
authors.affiliation: Department of Neurology, Oslo University Hospital, Oslo, Norway.|Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: H F
authors.initials: HF
authors.lastname: Harbo
authors.affiliation: Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
authors.forename: A
authors.initials: A
authors.lastname: Spurkland
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005260:Female; D020690:GTPase-Activating Proteins / Q000819:agonists / Q000097:blood / Q000235:genetics*; D015870:Gene Expression; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000037:antagonists & inhibitors / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D061251:Primary Cell Culture; D018167:Receptors, Calcitriol / Q000097:blood / Q000235:genetics*; D020218:Response Elements; D014807:Vitamin D / Q000097:blood / Q000494:pharmacology*
chemical_list: D020690:GTPase-Activating Proteins; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D018167:Receptors, Calcitriol; C557017:TAGAP protein, human; C579457:VDR protein, human; D014807:Vitamin D