Abstract:
INTRODUCTION: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.
journal_name
CNS Neurosci Therjournal_title
CNS neuroscience & therapeuticsauthors
Torre-Fuentes L,Matías-Guiu JA,Pytel V,Montero-Escribano P,Maietta P,Álvarez S,Gómez-Pinedo U,Matías-Guiu Jdoi
10.1111/cns.13456subject
Has Abstractpub_date
2020-11-01 00:00:00pages
1178-1184issue
11eissn
1755-5930issn
1755-5949journal_volume
26pub_type
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