Multiple sclerosis (relapsing-remitting) increases activation of Vitamin D Receptor by 6.6 X
Vitamin D receptor gene is epigenetically altered and transcriptionally up-regulated in multiple sclerosis - March 2017
PLoS One. 2017 Mar 29;12(3):e0174726. doi: 10.1371/journal.pone.0174726. eCollection 2017.
Ayuso T1, Aznar P2, Soriano L3, Olaskoaga A2, Roldán M3, Otano M1, Ajuria I1, Soriano G1, Lacruz F1, Mendioroz M2,3.
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OBJECTIVE:
Vitamin D deficiency has been linked to increased risk of multiple sclerosis (MS) and poor outcome. However, the specific role that vitamin D plays in MS still remains unknown. In order to identify potential mechanisms underlying vitamin D effects in MS, we profiled epigenetic changes in vitamin D receptor (VDR) gene to identify genomic regulatory elements relevant to MS pathogenesis.
METHODS:
Human T cells derived from whole blood by negative selection were isolated in a set of 23 relapsing-remitting MS (RRMS) patients and 12 controls matched by age and gender. DNA methylation levels were assessed by bisulfite cloning sequencing in two regulatory elements of VDR. mRNA levels were measured by RT-qPCR to assess changes in VDR expression between patients and controls.
RESULTS:
An alternative VDR promoter placed at exon 1c showed increased DNA methylation levels in RRMS patients (median 30.08%, interquartile range 19.2%) compared to controls (18.75%, 9.5%), p-value<0.05. Moreover, a 6.5-fold increase in VDR mRNA levels was found in RRMS patients compared to controls (p-value<0.001).
CONCLUSIONS:
An alternative promoter of the VDR gene shows altered DNA methylation levels in patients with multiple sclerosis, and it is associated with VDR mRNA upregulation. This locus may represent a candidate regulatory element in the genome relevant to MS pathogenesis.
PMID: 28355272 PMCID: PMC5371344 DOI: 10.1371/journal.pone.0174726