Bibliographic Details
| Title: |
Expression of risk genes linked to vitamin D receptor super-enhancer regions and their association with phenotype severity in multiple sclerosis |
| Authors: |
Sarah M. Orton, Amarpreet Sangha, Mehul Gupta, Kristina Martens, Luanne M. Metz, A. P. J. de Koning, Gerald Pfeffer |
| Source: |
Frontiers in Neurology, Vol 13 (2022) |
| Publisher Information: |
Frontiers Media S.A., 2022. |
| Publication Year: |
2022 |
| Collection: |
LCC:Neurology. Diseases of the nervous system |
| Subject Terms: |
multiple sclerosis, vitamin D deficiency, super-enhancers, vitamin D receptor (VDR), vitamin D, Neurology. Diseases of the nervous system, RC346-429 |
| More Details: |
Multiple sclerosis (MS) is a chronic debilitating neurological condition with a wide range of phenotype variability. A complex interplay of genetic and environmental factors contributes to disease onset and progression in MS patients. Vitamin D deficiency is a known susceptibility factor for MS, however the underlying mechanism of vitamin D-gene interactions in MS etiology is still poorly understood. Vitamin D receptor super-enhancers (VSEs) are enriched in MS risk variants and may modulate these environment-gene interactions. mRNA expression in total of 64 patients with contrasting MS severity was quantified in select genes. First, RNA-seq was performed on a discovery cohort (10 mild, 10 severe MS phenotype) and ten genes regulated by VSEs that have been linked to MS risk were analyzed. Four candidates showed a significant positive association (GRINA, PLEC, PARP10, and LRG1) in the discovery cohort and were then quantified using digital droplet PCR (ddPCR) in a validation cohort (33 mild, 11 severe MS phenotype). A significant differential expression persisted in the validation cohort for three of the VSE-MS genes: GRINA (p = 0.0138), LRG1 (p = 0.0157), and PLEC (p = 0.0391). In summary, genes regulated by VSE regions that contain known MS risk variants were shown to have differential expression based on disease severity (p |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
1664-2295 |
| Relation: |
https://www.frontiersin.org/articles/10.3389/fneur.2022.1064008/full; https://doaj.org/toc/1664-2295 |
| DOI: |
10.3389/fneur.2022.1064008 |
| Access URL: |
https://doaj.org/article/43770c769a174fb0b2b1d65ed810dbc3 |
| Accession Number: |
edsdoj.43770c769a174fb0b2b1d65ed810dbc3 |
| Database: |
Directory of Open Access Journals |
