Age-dependent VDR Peak DNA Methylation As a Mechanism for Latitude-dependent Multiple Sclerosis Risk

Overview

Journal Epigenetics Chromatin

Publisher Biomed Central

Specialties Biochemistry
Genetics

Date 2021 Feb 5

PMID 33541415

Citations 4

Authors

Lawrence T C Ong

Stephen D Schibeci

Nicole L Fewings

David R Booth

Grant P Parnell

Affiliations

Soon will be listed here.

Abstract

Background: The mechanisms linking UV radiation and vitamin D exposure to the risk of acquiring the latitude and critical period-dependent autoimmune disease, multiple sclerosis, is unclear. We examined the effect of vitamin D on DNA methylation and DNA methylation at vitamin D receptor binding sites in adult and paediatric myeloid cells. This was accomplished through differentiating CD34+ haematopoietic progenitors into CD14+ mononuclear phagocytes, in the presence and absence of calcitriol.

Results: Few DNA methylation changes occurred in cells treated with calcitriol. However, several VDR-binding sites demonstrated increased DNA methylation in cells of adult origin when compared to cells of paediatric origin. This phenomenon was not observed at other transcription factor binding sites. Genes associated with these sites were enriched for intracellular signalling and cell activation pathways involved in myeloid cell differentiation and adaptive immune system regulation.

Conclusion: These results suggest vitamin D exposure at critical periods during development may contribute to latitude-related differences in autoimmune disease incidence.

Citing Articles

DNA Methylation Signatures of Multiple Sclerosis Occur Independently of Known Genetic Risk and Are Primarily Attributed to B Cells and Monocytes.

Xavier A, Maltby V, Ewing E, Campagna M, Burnard S, Tegner J Int J Mol Sci. 2023; 24(16).

PMID: 37628757 PMC: 10454485. DOI: 10.3390/ijms241612576.

Vitamin D Metabolism Genes Are Differentially Methylated in Individuals with Chronic Knee Pain.

Strath L, Meng L, Rani A, Huo Z, Foster T, Fillingim R Lifestyle Genom. 2023; 16(1):98-105.

PMID: 36854277 PMC: 10493864. DOI: 10.1159/000529823.

From the prodromal stage of multiple sclerosis to disease prevention.

Marrie R, Allegretta M, Barcellos L, Bebo B, Calabresi P, Correale J Nat Rev Neurol. 2022; 18(9):559-572.

PMID: 35840705 DOI: 10.1038/s41582-022-00686-x.

Contribution of Dysregulated DNA Methylation to Autoimmunity.

Funes S, Fernandez-Fierro A, Rebolledo-Zelada D, Mackern-Oberti J, Kalergis A Int J Mol Sci. 2021; 22(21).

PMID: 34769338 PMC: 8584328. DOI: 10.3390/ijms222111892.

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