Mohamad Karaky1, Antonio Alcina2, María Fedetz1, Cristina Barrionuevo1, Victor Potenciano1, Concepción Delgado3, Guillermo Izquierdo4, Fuencisla Matesanz1. 1. Department of Cell Biology and Immunology, Instituto de Parasitología y Biomedicina "López Neyra" (IPBLN-CSIC), Granada, Spain. 2. 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. 3. Centro Regional de Transfusión Sanguínea Granada-Almería (CRTS), Granada, Spain. 4. Unidad de Esclerosis Múltiple, Hospital Universitario Virgen Macarena, Sevilla, Spain.
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.
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.
Authors: Mark B Meyer; Nancy A Benkusky; Martin Kaufmann; Seong Min Lee; Robert R Redfield; Glenville Jones; J Wesley Pike Journal: J Biol Chem Date: 2019-05-03 Impact factor: 5.157
Authors: Diego Fernández-Lázaro; Juan Luis García Hernández; Eva Lumbreras; Juan Mielgo-Ayuso; Jesús Seco-Calvo Journal: Int J Mol Sci Date: 2022-10-06 Impact factor: 6.208