{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T03:49:44Z","timestamp":1790480984795,"version":"4.1.0"},"reference-count":43,"publisher":"FapUNIFESP (SciELO)","issue":"3","license":[{"start":{"date-parts":[[2019,3,1]],"date-time":"2019-03-01T00:00:00Z","timestamp":1551398400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,3,1]],"date-time":"2019-03-01T00:00:00Z","timestamp":1551398400000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,3,1]],"date-time":"2019-03-01T00:00:00Z","timestamp":1551398400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arq. Neuro-Psiquiatr."],"abstract":"<jats:p>ABSTRACT It is currently unknown how genetic factors may influence the clinical course of multiple sclerosis (MS). Objective: We examined the impact of CIITA polymorphisms \u2212168A\/G (rs3087456) and +1614G\/C (rs4774) on the risk of disability progression, severity and on responses to first-line immunomodulator treatments. Methods: Genomic DNA was extracted from blood samples. We used ABI3730xl and GeneMapper v.4.0 software to identify genotype variations. All patients were followed up and clinically reassessed at three-month intervals. Disability progression was measured by the Expanded Disability Status Scale and disease severity by the Multiple Sclerosis Spasticity Scale (MSSS). Results: We included 37 men and 80 women. We found no evidence regarding the influence of the single nucleotide polymorphisms studied in the Expanded Disability Status Scale or therapeutic response of the evaluated drugs. We performed a logistic regression analysis with the MSSS and found that a less severe MS course was associated with wild type CIITA \u2212168AA and CIITA +1614GG, as the chance of the patient progressing to MSSS2 and MSSS3 decreased in 61% and 75% with CIITA \u2212168AA and 66% and 75% with CIITA +1614GG, respectively (p &lt; 0.0001). Although less significant, the CIITA +1614 GC also pointed to a less severe MS course and the chance of the patient progressing to MSSS3 decreased 79% (p = 0.015). We also observed that the CIITA \u2212168GG genotype was more frequent in MSSS2 and MSSS3 and had 40% lower odds ratio to becoming more severe MS. Conclusion: These data suggest that CIITA \u2212168AA, CIITA +1614GG and CIITA +1614 GC polymorphisms may be associated with a better MS clinical course. This knowledge may be useful for a better understanding of MS and its therapeutic management.<\/jats:p>","DOI":"10.1590\/0004-282x20190026","type":"journal-article","created":{"date-parts":[[2019,4,3]],"date-time":"2019-04-03T23:35:53Z","timestamp":1554334553000},"page":"166-173","source":"Crossref","is-referenced-by-count":11,"title":["Polymorphisms in the CIITA \u2212168A\/G (rs3087456) and CIITA +1614G\/C (rs4774) may influence severity in multiple sclerosis patients"],"prefix":"10.1590","volume":"77","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7212-5043","authenticated-orcid":false,"given":"Val\u00e9ria Coelho Santa Rita","family":"Pereira","sequence":"first","affiliation":[{"name":"Universidade Federal do Rio de Janeiro, Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5201-0927","authenticated-orcid":false,"given":"Fabr\u00edcia Lima","family":"Fontes-Dantas","sequence":"additional","affiliation":[{"name":"Universidade Federal do Estado do Rio de Janeiro, Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4048-3900","authenticated-orcid":false,"given":"Eduardo Ribeiro","family":"Paradela","sequence":"additional","affiliation":[{"name":"Universidade Federal do Estado do Rio de Janeiro, Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8275-3801","authenticated-orcid":false,"given":"Fab\u00edola Rachid","family":"Malfetano","sequence":"additional","affiliation":[{"name":"Universidade Federal do Rio de Janeiro, Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3555-5693","authenticated-orcid":false,"given":"Simone de Souza Batista","family":"Scherpenhuijzen","sequence":"additional","affiliation":[{"name":"Universidade Federal do Rio de Janeiro, Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9728-7279","authenticated-orcid":false,"given":"Let\u00edcia F\u00eazer","family":"Mansur","sequence":"additional","affiliation":[{"name":"Universidade Federal do Estado do Rio de Janeiro, Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7784-9905","authenticated-orcid":false,"given":"Ronir Raggio","family":"Luiz","sequence":"additional","affiliation":[{"name":"Universidade Federal do Rio de Janeiro, Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3379-8632","authenticated-orcid":false,"given":"Andr\u00e9 Peres De","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Universidade Federal do Estado do Rio de Janeiro, Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8246-7891","authenticated-orcid":false,"given":"Jo\u00e3o Gabriel Dib","family":"Farinhas","sequence":"additional","affiliation":[{"name":"Universidade Federal do Estado do Rio de Janeiro, Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0140-9548","authenticated-orcid":false,"given":"\u00c2ngelo","family":"Maiolino","sequence":"additional","affiliation":[{"name":"Universidade Federal do Rio de Janeiro, Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1538-6730","authenticated-orcid":false,"given":"Soniza Vieira","family":"Alves-Leon","sequence":"additional","affiliation":[{"name":"Universidade Federal do Rio de Janeiro, Brasil; Universidade Federal do Estado do Rio de Janeiro, Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"530","published-online":{"date-parts":[[2019,3]]},"reference":[{"issue":"13","key":"ref1","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1056\/NEJM200009283431307","article-title":"Multiple sclerosis","volume":"343","author":"Noseworthy JH","year":"2000","journal-title":"N Engl J Med"},{"issue":"11","key":"ref2","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1038\/nrneurol.2012.198","article-title":"The initiation and prevention of multiple sclerosis","volume":"8","author":"Ascherio A","year":"2012","journal-title":"Nat Rev Neurol"},{"key":"ref3","first-page":"1","article-title":"The genetics of multiple sclerosis","volume":"51","author":"Hillert J","year":"2010","journal-title":"Results Probl Cell Differ"},{"issue":"3","key":"ref4","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1212\/WNL.0000000000000560","article-title":"Defining the clinical course of multiple sclerosis: the 2013 revisions","volume":"83","author":"Lublin FD","year":"2014","journal-title":"Neurology"},{"issue":"11","key":"ref5","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1212\/WNL.33.11.1444","article-title":"Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS)","volume":"33","author":"Kurtzke JF","year":"1983","journal-title":"Neurology"},{"issue":"7","key":"ref6","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1212\/01.WNL.0000156155.19270.F8","article-title":"Multiple Sclerosis Severity Score: using disability and disease duration to rate disease severity","volume":"64","author":"Roxburgh RH","year":"2005","journal-title":"Neurology"},{"issue":"11","key":"ref7","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1136\/jnnp-2016-313722","article-title":"Role of genetic susceptibility variants in predicting clinical course in multiple sclerosis: a cohort study","volume":"87","author":"Pan G","year":"2016","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"4","key":"ref8","doi-asserted-by":"crossref","DOI":"10.1212\/NXG.0000000000000087","article-title":"Multiple sclerosis risk loci and disease severity in 7,125 individuals from 10 studies","volume":"2","author":"George MF","year":"2016","journal-title":"Neurol Genet"},{"issue":"18","key":"ref9","doi-asserted-by":"crossref","first-page":"2813","DOI":"10.1093\/hmg\/ddl223","article-title":"Heterogeneity at the HLA-DRB1 locus and risk for multiple sclerosis","volume":"15","author":"Barcellos LF","year":"2006","journal-title":"Hum Mol Genet"},{"issue":"5","key":"ref10","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1111\/j.1600-0404.2006.00750.x","article-title":"Ethnicity-dependent association of HLA DRB1-DQA1-DQB1 alleles in Brazilian multiple sclerosis patients","volume":"115","author":"Alves-Leon SV","year":"2007","journal-title":"Acta Neurol Scand"},{"issue":"3","key":"ref11","article-title":"European ancestry predominates in neuromyelitis optica and multiple sclerosis patients from Brazil","volume":"8","author":"Brum DG","year":"2013","journal-title":"PLoS One"},{"issue":"9","key":"ref12","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1101\/gad.14.9.1156","article-title":"CIITA is a transcriptional coactivator that is recruited to MHC class II promoters by multiple synergistic interactions with an enhanceosome complex","volume":"14","author":"Masternak K","year":"2000","journal-title":"Genes Dev"},{"issue":"11","key":"ref13","doi-asserted-by":"crossref","first-page":"2331","DOI":"10.1093\/hmg\/ddq101","article-title":"International Multiple Sclerosis Genetics Consortium. 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