{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T08:43:24Z","timestamp":1790757804415,"version":"4.1.0"},"reference-count":37,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2023,5,28]],"date-time":"2023-05-28T00:00:00Z","timestamp":1685232000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000890","name":"National Multiple Sclerosis Society","doi-asserted-by":"publisher","award":["RG\u20101707\u201028657"],"award-info":[{"award-number":["RG\u20101707\u201028657"]}],"id":[{"id":"10.13039\/100000890","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000890","name":"National Multiple Sclerosis Society","doi-asserted-by":"publisher","award":["JF\u20101808\u201032223"],"award-info":[{"award-number":["JF\u20101808\u201032223"]}],"id":[{"id":"10.13039\/100000890","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and purpose<\/jats:title><jats:p>Vitamin D is considered to play a role in multiple sclerosis (MS) etiopathogenesis. A polymorphism in the<jats:italic>CYP24A1<\/jats:italic>gene, rs2762943, was recently identified that was associated with an increased MS risk.<jats:italic>CYP24A1<\/jats:italic>encodes a protein involved in the catabolism of the active form of vitamin D. The immunological effects of carrying the rs2762943 risk allele were investigated, as well as its role as genetic modifier.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Serum levels of 25\u2010hydroxyvitamin D and 1,25\u2010dihydroxyvitamin D (1,25(OH)<jats:sub>2<\/jats:sub>D) were measured in a cohort of 167 MS patients. In a subgroup of patients, expression levels of major histocompatibility complex class II and co\u2010stimulatory molecules were determined by flow cytometry, and serum levels of pro\u2010inflammatory (interferon gamma, granulocyte macrophage colony\u2010stimulating factor, C\u2010X\u2010C motif chemokine ligand 13) and anti\u2010inflammatory (interleukin 10) cytokines and neurofilament light chain were measured by single\u2010molecule array assays. The effect of the rs2762943 polymorphism on disease activity and disability measures was evaluated in 340 MS patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared to non\u2010carriers, carriers of the rs2762943 risk allele were characterized by reduced levels of 1,25(OH)<jats:sub>2<\/jats:sub>D (<jats:italic>p<\/jats:italic>\u2009=\u20090.0001) and elevated levels of interferon gamma (<jats:italic>p<\/jats:italic>\u2009=\u20090.03) and granulocyte macrophage colony\u2010stimulating factor (<jats:italic>p<\/jats:italic>\u2009=\u20090.008), whereas no significant differences were observed for the other markers. The presence of the rs2762943 risk allele had no significant impact on disease activity and disability outcomes during follow\u2010up. However, risk allele carriers were younger at disease onset (<jats:italic>p<\/jats:italic>\u2009=\u20090.04).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These findings suggest that the<jats:italic>CYP24A1<\/jats:italic>rs2762943 polymorphism plays a more important role in MS susceptibility than in disease prognosis and is associated with lower 1,25(OH)<jats:sub>2<\/jats:sub>D levels and a heightened pro\u2010inflammatory environment in MS patients.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ene.15866","type":"journal-article","created":{"date-parts":[[2023,5,15]],"date-time":"2023-05-15T06:33:50Z","timestamp":1684132430000},"page":"2401-2410","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The<i>CYP24A1<\/i>gene variant rs2762943 is associated with low serum 1,25\u2010dihydroxyvitamin D levels in multiple sclerosis patients"],"prefix":"10.1111","volume":"30","author":[{"given":"Sunny","family":"Malhotra","sequence":"first","affiliation":[{"name":"Servei de Neurologia\u2010Neuroimmunologia, Centre d'Esclerosi M\u00faltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR) Hospital Universitari Vall d'Hebron, Universitat Aut\u00f2noma de Barcelona Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7981-2228","authenticated-orcid":false,"given":"Luciana","family":"Midaglia","sequence":"additional","affiliation":[{"name":"Servei de Neurologia\u2010Neuroimmunologia, Centre d'Esclerosi M\u00faltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR) Hospital Universitari Vall d'Hebron, Universitat Aut\u00f2noma de Barcelona Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar","family":"Chuquisana","sequence":"additional","affiliation":[{"name":"Department of Neurology with Institute of Translational Neurology University Hospital M\u00fcnster M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaos A.","family":"Patsopoulos","sequence":"additional","affiliation":[{"name":"Systems Biology and Computer Science Program, Department of Neurology, Ann Romney Center for Neurological Diseases Brigham and Women's Hospital Boston Massachusetts USA"},{"name":"Harvard Medical School Boston Massachusetts USA"},{"name":"Broad Institute of Harvard and Massachusetts Institute of Technology Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roser","family":"Ferrer","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica Hospital Universitari Vall D'Hebron, Universitat Aut\u00f2noma de Barcelona Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Giralt","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica 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