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The multiple sclerosis-associated regulatory variant rs10877013 affects expression of CYP27B1 and VDR under inflammatory or vitamin D stimuli.
- Source :
-
Multiple sclerosis (Houndmills, Basingstoke, England) [Mult Scler] 2016 Jul; Vol. 22 (8), pp. 999-1006. Date of Electronic Publication: 2015 Oct 14. - Publication Year :
- 2016
-
Abstract
- Background: Vitamin D deficit is considered an important risk factor for many inflammatory and autoimmune diseases.<br />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.<br />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).<br />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.<br />Conclusions: The MS-associated variant rs10877013 is a genetic determinant that affects the functioning of the vitamin D system linking environmental and genetic factors.<br /> (© The Author(s), 2015.)
- Subjects :
- 25-Hydroxyvitamin D3 1-alpha-Hydroxylase metabolism
Cell Line
Gene Expression Regulation
Humans
Monocytes enzymology
Monocytes immunology
Multiple Sclerosis diagnosis
Multiple Sclerosis enzymology
Multiple Sclerosis immunology
Receptors, Calcitriol agonists
Receptors, Calcitriol metabolism
Time Factors
Vitamin D3 24-Hydroxylase genetics
Vitamin D3 24-Hydroxylase metabolism
25-Hydroxyvitamin D3 1-alpha-Hydroxylase genetics
Interferon-gamma pharmacology
Lipopolysaccharides pharmacology
Monocytes drug effects
Multiple Sclerosis genetics
Polymorphism, Single Nucleotide
Receptors, Calcitriol genetics
Vitamin D pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1477-0970
- Volume :
- 22
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Multiple sclerosis (Houndmills, Basingstoke, England)
- Publication Type :
- Academic Journal
- Accession number :
- 26466946
- Full Text :
- https://doi.org/10.1177/1352458515610208