{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T10:48:57Z","timestamp":1788518937506,"version":"build-2803163510"},"reference-count":25,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2020,9,20]],"date-time":"2020-09-20T00:00:00Z","timestamp":1600560000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>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\u2010\u03b1, 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used whole\u2010exome sequencing to study genes coding for TNF\u2010\u03b1 receptors and ligands, and proteins promoting TNF\u2010\u03b1 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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\u2010\u03b1 variants rs1041981 and rs2229094 and LT\u2010\u03b2 variant rs4647197 were associated with MS and that LT\u2010\u03b2 variant rs4647183 was associated with other autoimmune diseases. The association between autoimmune disease and <jats:italic>TNFAIP2<\/jats:italic> variant rs1132339 is particularly noteworthy, as is the fact that <jats:italic>TNFAIP6<\/jats:italic> variant rs1046668 appears to follow a recessive inheritance pattern.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings support the idea that the risk of familial MS is associated with variants of signaling pathways, including those involving TNF\u2010\u03b1.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.13456","type":"journal-article","created":{"date-parts":[[2020,9,20]],"date-time":"2020-09-20T10:04:57Z","timestamp":1600596297000},"page":"1178-1184","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Variants of genes encoding TNF receptors and ligands and proteins regulating TNF activation in familial multiple sclerosis"],"prefix":"10.1111","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4878-584X","authenticated-orcid":false,"given":"Laura","family":"Torre\u2010Fuentes","sequence":"first","affiliation":[{"name":"Laboratory of Neurobiology Institute of Neurosciences IdISSC, Hospital Cl\u00ednico San Carlos Universidad Complutense de Madrid Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5520-2708","authenticated-orcid":false,"given":"Jordi A.","family":"Mat\u00edas\u2010Guiu","sequence":"additional","affiliation":[{"name":"Department of Neurology Institute of Neurosciences IdISSC, Hospital Cl\u00ednico San Carlos Universidad Complutense de Madrid Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2518-338X","authenticated-orcid":false,"given":"Vanesa","family":"Pytel","sequence":"additional","affiliation":[{"name":"Laboratory of Neurobiology Institute of Neurosciences IdISSC, Hospital Cl\u00ednico San Carlos Universidad Complutense de Madrid Madrid Spain"},{"name":"Department of Neurology Institute of Neurosciences IdISSC, Hospital Cl\u00ednico San Carlos Universidad Complutense de Madrid Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3615-7678","authenticated-orcid":false,"given":"Paloma","family":"Montero\u2010Escribano","sequence":"additional","affiliation":[{"name":"Laboratory of Neurobiology Institute of Neurosciences IdISSC, Hospital Cl\u00ednico San Carlos Universidad Complutense de Madrid Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9446-8063","authenticated-orcid":false,"given":"Paolo","family":"Maietta","sequence":"additional","affiliation":[{"name":"Nimgenetics Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"\u00c1lvarez","sequence":"additional","affiliation":[{"name":"Nimgenetics Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3097-5557","authenticated-orcid":false,"given":"Ulises","family":"G\u00f3mez\u2010Pinedo","sequence":"additional","affiliation":[{"name":"Laboratory of Neurobiology Institute of Neurosciences IdISSC, Hospital Cl\u00ednico San Carlos Universidad Complutense de Madrid Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8162-9043","authenticated-orcid":false,"given":"Jorge","family":"Mat\u00edas\u2010Guiu","sequence":"additional","affiliation":[{"name":"Laboratory of Neurobiology Institute of Neurosciences IdISSC, Hospital Cl\u00ednico San Carlos Universidad Complutense de Madrid Madrid Spain"},{"name":"Department of Neurology Institute of Neurosciences IdISSC, 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