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The multiple sclerosis-associated regulatory variant rs10877013 affects expression of CYP27B1 and VDR under inflammatory or vitamin D stimuli

AuthorsKaraky, Mohamad; Alcina, Antonio; Fedetz, María; Barrionuevo, Cristina; Potenciano, Víctor; Delgado, Concepción; Izquierdo, Guillermo; Matesanz, F.
KeywordsVitamin D
functional variant rs10877013
gene expression regulation
Issue DateJul-2016
PublisherSage Publications
CitationMultiple Sclerosis Journal
AbstractBACKGROUND: Vitamin D deficit is considered an important risk factor for many inflammatory and autoimmune diseases. OBJECTIVE: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: The MS-associated variant rs10877013 is a genetic determinant that affects the functioning of the vitamin D system linking environmental and genetic factors.
Publisher version (URL)http://dx.doi.org/10.1177/1352458515610208
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