The multiple sclerosis-associated regulatory variant rs10877013 affects expression of CYP27B1 and VDR under inflammatory or vitamin D stimuli.
Mult Scler
; 22(8): 999-1006, 2016 07.
Article
em En
| MEDLINE
| ID: mdl-26466946
ABSTRACT
BACKGROUND:
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vitamina D
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Monócitos
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Lipopolissacarídeos
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Interferon gama
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Receptores de Calcitriol
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Polimorfismo de Nucleotídeo Único
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25-Hidroxivitamina D3 1-alfa-Hidroxilase
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Esclerose Múltipla
Tipo de estudo:
Diagnostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Mult Scler
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Espanha