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dc.contributor.author | Swaminathan, B. | - |
dc.contributor.author | Cuapio, Angélica | - |
dc.contributor.author | Alloza, I. | - |
dc.contributor.author | Matesanz, F. | - |
dc.contributor.author | Alcina, Antonio | - |
dc.contributor.author | García-Barcina, María | - |
dc.contributor.author | Fedetz, María | - |
dc.contributor.author | Fernández, Óscar | - |
dc.contributor.author | Lucas, Miguel | - |
dc.contributor.author | Órpez, Teresa | - |
dc.contributor.author | Pinto-Medel, María Jesús | - |
dc.contributor.author | Otaegui, David | - |
dc.contributor.author | Olascoaga, J. | - |
dc.contributor.author | Urcelay, Elena | - |
dc.contributor.author | Ortiz, Miguel A. | - |
dc.contributor.author | Arroyo, R. | - |
dc.contributor.author | Oksenberg, J. R. | - |
dc.contributor.author | Antigüedad, A. | - |
dc.contributor.author | Tolosa, Eva | - |
dc.contributor.author | Vandenbroeck, Koen | - |
dc.date.accessioned | 2013-11-08T12:34:59Z | - |
dc.date.available | 2013-11-08T12:34:59Z | - |
dc.date.issued | 2013-04-24 | - |
dc.identifier.citation | PLoS ONE | es_ES |
dc.identifier.issn | 1932-6203 | - |
dc.identifier.uri | http://hdl.handle.net/10261/85887 | - |
dc.description | Art. nº e62376; v. 8; issue 4 | es_ES |
dc.description.abstract | CD6 has recently been identified and validated as risk gene for multiple sclerosis (MS), based on the association of a single nucleotide polymorphism (SNP), rs17824933, located in intron 1. CD6 is a cell surface scavenger receptor involved in T-cell activation and proliferation, as well as in thymocyte differentiation. In this study, we performed a haptag SNP screen of the CD6 gene locus using a total of thirteen tagging SNPs, of which three were non-synonymous SNPs, and replicated the recently reported GWAS SNP rs650258 in a Spanish-Basque collection of 814 controls and 823 cases. Validation of the six most strongly associated SNPs was performed in an independent collection of 2265 MS patients and 2600 healthy controls. We identified association of haplotypes composed of two non-synonymous SNPs [rs11230563 (R225W) and rs2074225 (A257V)] in the 2nd SRCR domain with susceptibility to MS (Pmax(T) permutation=161024). The effect of these haplotypes on CD6 surface expression and cytokine secretion was also tested. The analysis showed significantly different CD6 expression patterns in the distinct cell subsets, i.e. – CD4+ naı¨ve cells, P = 0.0001; CD8+ naı¨ve cells, P,0.0001; CD4+ and CD8+ central memory cells, P = 0.01 and 0.05, respectively; and natural killer T (NKT) cells, P = 0.02; with the protective haplotype (RA) showing higher expression of CD6. However, no significant changes were observed in natural killer (NK) cells, effector memory and terminally differentiated effector memory T cells. Our findings reveal that this new MS-associated CD6 risk haplotype significantly modifies expression of CD6 on CD4+ and CD8+ T cells. | es_ES |
dc.description.abstract | doi:10.1371/journal.pone.0062376 | es_ES |
dc.description.sponsorship | European Community 212877; Gobierno Vasco (Grupos de Investigacion del Sistema Universitario Vasco) IT512-10;Ministerio de Ciencia e Innovacion - FEDER SAF2009-11491;FIS_FEDER CP10/00526 ;Junta de Andalucia-FEDER P07-CVI-02551 | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Public Library of Science | es_ES |
dc.relation.isversionof | Publisher's version | - |
dc.rights | openAccess | es_ES |
dc.subject | Anti-CD6 monoclonal-antibody | es_ES |
dc.subject | Genome-wide association | es_ES |
dc.subject | Central-nervous-system | es_ES |
dc.subject | Helper 17 cells | es_ES |
dc.title | Fine Mapping and Functional Analysis of the Multiple Sclerosis Risk Gene CD6 | es_ES |
dc.type | artículo | es_ES |
dc.description.peerreviewed | Peer reviewed | es_ES |
dc.relation.publisherversion | http://www.plosone.org/article/comments/info%3Adoi%2F10.1371%2Fjournal.pone.0062376;jsessionid=3721920BD7E702A21F37F49401CBACC7 | es_ES |
dc.relation.publisherversion | doi:10.1371/journal.pone.0062376 | es_ES |
dc.identifier.pmid | 23638056 | - |
dc.type.coar | http://purl.org/coar/resource_type/c_6501 | es_ES |
item.cerifentitytype | Publications | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.grantfulltext | open | - |
item.openairetype | artículo | - |
item.fulltext | With Fulltext | - |
item.languageiso639-1 | en | - |
Aparece en las colecciones: | (IPBLN) Artículos |
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FineMapping.pdf | 890,54 kB | Adobe PDF | Visualizar/Abrir |
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