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

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+IFN3) 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+IFN3 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.