Variants of genes encoding TNF receptors and ligands and proteins regulating TNF activation in familial multiple sclerosis.
TNF
TNF-α
genetics
multiple sclerosis
whole-exome sequencing
Journal
CNS neuroscience & therapeutics
ISSN: 1755-5949
Titre abrégé: CNS Neurosci Ther
Pays: England
ID NLM: 101473265
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
17
10
2019
revised:
25
08
2020
accepted:
26
08
2020
pubmed:
21
9
2020
medline:
26
10
2021
entrez:
20
9
2020
Statut:
ppublish
Résumé
Numerous genetic variants have been associated with susceptibility to multiple sclerosis (MS). Variants located in genes involved in specific pathways, such as those affecting TNF-α, can contribute to the risk of MS. The purpose of this study was to determine whether variants of these genes are associated with greater risk of MS. We used whole-exome sequencing to study genes coding for TNF-α receptors and ligands, and proteins promoting TNF-α expression in 116 individuals from 19 families including at least two MS patients. We compared patients with MS, patients with other autoimmune diseases, and healthy individuals. Greater polymorphism was observed in several genes in families with familial MS compared to the general population; this may reflect greater susceptibility to autoimmune diseases. Pedigree analysis also revealed that LT-α variants rs1041981 and rs2229094 and LT-β variant rs4647197 were associated with MS and that LT-β variant rs4647183 was associated with other autoimmune diseases. The association between autoimmune disease and TNFAIP2 variant rs1132339 is particularly noteworthy, as is the fact that TNFAIP6 variant rs1046668 appears to follow a recessive inheritance pattern. Our findings support the idea that the risk of familial MS is associated with variants of signaling pathways, including those involving TNF-α.
Identifiants
pubmed: 32951330
doi: 10.1111/cns.13456
pmc: PMC7564193
doi:
Substances chimiques
Ligands
0
Receptors, Tumor Necrosis Factor
0
Tumor Necrosis Factor-alpha
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1178-1184Informations de copyright
© 2020 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.
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