title: The multiple sclerosis-associated regulatory variant rs10877013 affects expression of CYP27B1 and VDR under inflammatory or vitamin D stimuli.
abstract: Vitamin D deficit is considered an important risk factor for many inflammatory and autoimmune diseases.
  
  
  
  To investigate the influence of the multiple sclerosis (MS)-associated regulatory variant rs10877013 on the expression of genes involved in vitamin D activation (CYP27B1), vitamin D receptor (VDR), and vitamin D degradation (CYP24A1) under inflammatory environment or vitamin D.
  
  
  
  We used lipopolysaccharide and interferon-gamma (LPS+IFNγ) activated monocytes from 119 individuals and vitamin D-stimulated lymphoblastoid cell lines (LCLs, n = 109) of 1000 genomes to quantify the mRNA expression of vitamin D genes by quantitative reverse transcription polymerase chain reaction (RT-qPCR).
  
  
  
  We found that CYP27B1 mRNA expression level was associated with the rs10877013 genotypes (p = 5.0E-6) in LPS+IFNγ treated monocytes, but not in vitamin D-stimulated LCLs. Inversely, rs10877013 genotypes were associated with VDR expression in LCLs (p = 6.0E-4) but not in monocytes. Finally, CYP24A1 was highly induced by the active form of vitamin D and its expression correlated with the expression of VDR in LCLs but neither the MS-associated variant in the region (rs2248359) nor any other variant located in 1 Mb around CYP24A1 was associated with its expression.
  
  
  
  The MS-associated variant rs10877013 is a genetic determinant that affects the functioning of the vitamin D system linking environmental and genetic factors.
authors.affiliation: Department of Cell Biology and Immunology, Instituto de Parasitología y Biomedicina "López Neyra" (IPBLN-CSIC), Granada, Spain.
authors.forename: Mohamad
authors.initials: M
authors.lastname: Karaky
authors.affiliation: Department of Cell Biology and Immunology, Instituto de Parasitología y Biomedicina "López Neyra" (IPBLN-CSIC), Granada, Spain pulgoso@ipb.csic.es lindo@ipb.csic.es.
authors.forename: Antonio
authors.initials: A
authors.lastname: Alcina
authors.affiliation: Department of Cell Biology and Immunology, Instituto de Parasitología y Biomedicina "López Neyra" (IPBLN-CSIC), Granada, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Fedetz
authors.affiliation: Department of Cell Biology and Immunology, Instituto de Parasitología y Biomedicina "López Neyra" (IPBLN-CSIC), Granada, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Barrionuevo
authors.affiliation: Department of Cell Biology and Immunology, Instituto de Parasitología y Biomedicina "López Neyra" (IPBLN-CSIC), Granada, Spain.
authors.forename: Victor
authors.initials: V
authors.lastname: Potenciano
authors.affiliation: Centro Regional de Transfusión Sanguínea Granada-Almería (CRTS), Granada, Spain.
authors.forename: Concepción
authors.initials: C
authors.lastname: Delgado
authors.affiliation: Unidad de Esclerosis Múltiple, Hospital Universitario Virgen Macarena, Sevilla, Spain.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Izquierdo
authors.affiliation: Department of Cell Biology and Immunology, Instituto de Parasitología y Biomedicina "López Neyra" (IPBLN-CSIC), Granada, Spain.
authors.forename: Fuencisla
authors.initials: F
authors.lastname: Matesanz
mesh_terms: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D005786:Gene Expression Regulation; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D009103:Multiple Sclerosis / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics* / Q000276:immunology; D020641:Polymorphism, Single Nucleotide; D018167:Receptors, Calcitriol / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D013997:Time Factors; D014807:Vitamin D / Q000494:pharmacology*; D065668:Vitamin D3 24-Hydroxylase / Q000235:genetics / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; D018167:Receptors, Calcitriol; C579457:VDR protein, human; D014807:Vitamin D; D007371:Interferon-gamma; C585549:CYP24A1 protein, human; D065668:Vitamin D3 24-Hydroxylase; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; C000600378:CYP27B1 protein, human
keywords: CYP24A1; CYP27B1; VDR; Vitamin D; functional variant rs10877013; gene expression regulation