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

Introduction: Recent evidence suggests that vitamin D may interact with the epigenome and play a role in the pain experience. In order for proper functioning to occur, there must be an adequate level of vitamin D present, made possible by enzymatic reactions that allow vitamin D to be biologically active. The purpose of this study was to explore the epigenetic landscape of genes involved in vitamin D metabolism in individuals with and without chronic knee pain. Methods: Community-dwelling individuals recruited as part of a larger study focused on knee pain provided demographic, clinical, and pain-related information, as well as an intravenous blood sample to determine DNA methylation levels at CpG sites. Results: There were differences in DNA methylation between those with and without pain in genes that code for enzymes related to vitamin D metabolism: CYP27B1 (1-alpha-hydroxylase). There was also hypermethylation on the gene that codes for the vitamin D receptor (VDR). Conclusions: The presence of chronic pain is associated with epigenetic modifications in genes responsible for the expression of enzymes involved in vitamin D metabolism and cellular function. These results lay groundwork in understanding the mechanism underlying the association between vitamin D and chronic pain.