dc.contributor.author | Swaminathan, Bhairavi | |
dc.contributor.author | Cuapio, Angélica | |
dc.contributor.author | Alloza Moral, Iraide | |
dc.contributor.author | Matesanz, Fuencisla | |
dc.contributor.author | Alcina, Antonio | |
dc.contributor.author | García-Barcina, María | |
dc.contributor.author | Fedetz, María | |
dc.contributor.author | Fernández, Óscar | |
dc.contributor.author | Órpez, Teresa | |
dc.contributor.author | Pinto-Medel, Mº Jesús | |
dc.contributor.author | Otaegui Bichot, David | |
dc.contributor.author | Olascoaga, Javier | |
dc.contributor.author | Urcelay, Elena | |
dc.contributor.author | Ortiz, Miguel A. | |
dc.contributor.author | Arroyo, Rafael | |
dc.contributor.author | Oksenberg, Jorge R. | |
dc.contributor.author | Rodríguez-Antigüedad Zarranz, Alfredo | |
dc.contributor.author | Tolosa, Eva | |
dc.contributor.author | Vandenbroeck, Koen | |
dc.date.accessioned | 2013-06-18T10:17:54Z | |
dc.date.available | 2013-06-18T10:17:54Z | |
dc.date.issued | 2013 | |
dc.identifier.citation | PLoS ONE 8(4) : (2013) // e62376 | es |
dc.identifier.issn | 1932-6203 | |
dc.identifier.uri | http://hdl.handle.net/10810/10303 | |
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 |
dc.description.sponsorship | This work was supported by grants to K.V. from the European Community’s Seventh Framework Programme [FP7/2007–2013] under grant agreement
no. 212877 (UEPHA*MS; www.reem.es/uepha-ms/) and from the Gobierno Vasco (Grupos de Investigacio´n del Sistema Universitario Vasco; ref. IT512-10). B.S. and
A.C. are early-stage researchers of UEPHA*MS (No 2121877). Grants to A.A. and F.M. were provided by Ministerio de Ciencia e Innovacio´n - FEDER (SAF2009-11491)
and FIS_FEDER (CP10/00526), Junta de Andalucı´a-FEDER (P07-CVI-02551). | es |
dc.language.iso | eng | es |
dc.publisher | Public Library of Science | es |
dc.relation | info:eu-repo/grantAgreement/MICINN/SAF2009-11491 | |
dc.rights | info:eu-repo/semantics/openAccess | es |
dc.title | Fine mapping and functional analysis of the multiple sclerosis risk gene CD6 | es |
dc.type | info:eu-repo/semantics/article | es |
dc.rights.holder | 2013 Swaminathan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use,distribution, and reproduction in any medium, provided the original author and source are credited. | es |
dc.relation.publisherversion | http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0062376 | es |
dc.identifier.doi | 10.1371/journal.pone.0062376 | |
dc.departamentoes | Neurociencias | es_ES |
dc.departamentoeu | Neurozientziak | es_ES |
dc.subject.categoria | AGRICULTURAL AND BIOLOGICAL SCIENCES | |
dc.subject.categoria | BIOCHEMISTRY AND MOLECULAR BIOLOGY | |
dc.subject.categoria | MEDICINE | |