Exonic variants of genes related to the vitamin D signaling pathway in the families of familial multiple sclerosis using whole-exome next generation sequencing.
CYP24A1
PDIA3
VDR
cubilin
familial multiple sclerosis
megalin
vitamin D
whole-exome sequencing
Journal
Brain and behavior
ISSN: 2162-3279
Titre abrégé: Brain Behav
Pays: United States
ID NLM: 101570837
Informations de publication
Date de publication:
04 2019
04 2019
Historique:
received:
03
01
2019
revised:
27
02
2019
accepted:
06
03
2019
pubmed:
23
3
2019
medline:
18
12
2019
entrez:
23
3
2019
Statut:
ppublish
Résumé
Vitamin D (VD) deficiency has been associated with multiple sclerosis (MS) and other autoimmune diseases (AIDs). However, the effect of the genetics of VD on the risk of MS is subject to debate. This study focuses on genes linked to the VD signaling pathway in families with MS. The evaluation of gene variants in all the members of families could contribute to an additional knowledge on the information obtained from case-control studies that use nonrelated healthy people. We studied 94 individuals from 15 families including at least two patients with MS. We performed whole-exome next generation sequencing on all individuals and analyzed variants of the DHCR7, CYP2R1, CYP3A4, CYP27A1, GC, CYP27B1, LRP2, CUBN, DAB2, FCGR, RXR, VDR, CYP24A1, and PDIA3 genes. We also studied PTH, FGF23, METTL1, METTL21B, and the role of the linkage disequilibrium block on the long arm of chromosome 12, through analysis of the CDK4, TSFM, AGAP2, and AVIL genes. We compared patients with MS, other AIDs and unaffected members from different family types. The study described the variants in the VD signaling pathway that appear in families with at least two patients with MS. Some infrequent variants were detected in these families, but no significant difference was observed between patients with MS and/or other AIDs and unaffected family members in the frequency of these variants. Variants previously associated with MS in the literature were not observed in these families or were distributed similarly in patients and unaffected family members. The study of genes involved in the VD signaling pathway in families that include more than one patient with MS did not identify any variants that could explain the presence of the disease, suggesting that VD metabolism could probably play a role in MS more as an environmental factor rather than as a genetic factor. Our study also supports the analysis of cases and unaffected individuals within families in order to determine the influence of genetic factors.
Identifiants
pubmed: 30900415
doi: 10.1002/brb3.1272
pmc: PMC6456803
doi:
Substances chimiques
FGF23 protein, human
0
Vitamin D
1406-16-2
Fibroblast Growth Factor-23
7Q7P4S7RRE
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e01272Informations de copyright
© 2019 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.
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