Please use this identifier to cite or link to this item: http://hdl.handle.net/10668/1362
Título : Fine mapping and functional analysis of the multiple sclerosis risk gene CD6.
Autor : Swaminathan, Bhairavi
Cuapio, Angélica
Alloza, Iraide
Matesanz, Fuencisla
Alcina, Antonio
García-Barcina, Maria
Fedetz, Maria
Fernández, Oscar
Lucas, Miguel
Orpez, Teresa
Pinto-Medel, M Jesus
Otaegui, David
Olascoaga, Javier
Urcelay, Elena
Ortiz, Miguel A
Arroyo, Rafael
Oksenberg, Jorge R
Antigüedad, Alfredo
Tolosa, Eva
Vandenbroeck, Koen
Filiación: [Swaminathan,B; Alloza,I; Vandenbroeck,K] Neurogenomiks Laboratory, University of the Basque Country (UPV/EHU), Leioa, Spain. [Cuapio,A; Tolosa,E] Department of Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. [Matesanz,F; Alcina,A; Fedetz,M] Instituto de Parasitología y Biomedicina "López Neyra" Consejo Superior de Investigaciones Científicas (CSIC), Granada, Spain. [García-Barcina,M] Servicio de Genética, Hospital de Basurto, Bilbao, Spain. [Fernández,O] Department of Neurology, Institute of Clinical Neurosciences, Hospital Regional Universitario Carlos Haya, Málaga, Spain. [ Lucas,M] Unidad de Esclerosis Múltiple, Hospital Virgen Macarena, Sevilla, Spain. [Orpez,T; Pinto-Medel,MJ] Research Laboratory, Institute of Clinical Neurosciences, Hospital Regional Universitario Carlos Haya, Málaga, Spain. [Otaegui,D] Área de Neurociencias, Instituto de Investigación Sanitaria Biodonostia, San Sebastián, Spain. [ Olascoaga,J] Servicio de Neurología, Unidad de Esclerosis Múltiple, Hospital Donostia, San Sebastián, Spain. [Urcelay,E; Ortiz,MA] Immunology Department H. Clínico S. Carlos, Instituto de Investigación Sanitaria S. Carlos (IdISSC), Madrid, Spain. [Arroyo,R] Multiple Sclerosis Unit, Neurology Department H. Clínico S. Carlos, Instituto de Investigación Sanitaria S. Carlos (IdISSC), Madrid, Spain. [Oksenberg,JR] Department of Neurology, University of California San Francisco, San Francisco, California, United States of America. [Antigüedad,A] Servicio de Neurología, Hospital de Basurto, Bilbao, Spain. [Vandenbroeck,K] IKERBASQUE, Basque Foundation for Science, Bilbao, Spain
Palabras clave : Esclerosis múltiple
estudio de asociación genómica completa
Polimorfismo genético
Timocitos
Haplotipos
MeSH: Medical Subject Headings::Health Care::Environment and Public Health::Public Health::Epidemiologic Methods::Epidemiologic Research Design::Genome-Wide Association Study
Medical Subject Headings::Anatomy::Cells::Thymocytes
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genotype::Haplotypes
Medical Subject Headings::Diseases::Immune System Diseases::Autoimmune Diseases::Autoimmune Diseases of the Nervous System::Demyelinating Autoimmune Diseases, CNS::Multiple Sclerosis
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism, Genetic
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans
Fecha de publicación : 24-Apr-2013
Editorial : Public Library of Science
Cita Bibliográfica: Swaminathan B, Cuapio A, Alloza I, Matesanz F, Alcina A, García-Barcina M, et al. Fine mapping and functional analysis of the multiple sclerosis risk gene CD6. PLoS ONE. 2013; 8(4):e62376
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 2(nd) SRCR domain with susceptibility to MS (P max(T) permutation = 1×10(-4)). 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(+) naïve cells, P = 0.0001; CD8(+) naïve 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.
Descripción : Journal Article;
URI: http://hdl.handle.net/10668/1362
Versión del editor : http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0062376
DOI: 10.1371/journal.pone.0062376
ISSN : 1932-6203 (Online)
Appears in Collections:01- Artículos - Hospital Regional de Málaga
01- Artículos - Hospital Virgen Macarena

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