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Variants of genes encoding TNF receptors and ligands and proteins regulating TNF activation in familial multiple sclerosis
Author(s) -
TorreFuentes Laura,
MatíasGuiu Jordi A.,
Pytel Vanesa,
MonteroEscribano Paloma,
Maietta Paolo,
Álvarez Sara,
GómezPinedo Ulises,
MatíasGuiu Jorge
Publication year - 2020
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.13456
Subject(s) - multiple sclerosis , gene , receptor , tumor necrosis factor alpha , genetics , neuroscience , biology , computational biology , immunology
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. Methods 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. Results 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. Conclusions Our findings support the idea that the risk of familial MS is associated with variants of signaling pathways, including those involving TNF‐α.

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