Please use this identifier to cite or link to this item: http://hdl.handle.net/10668/489
Title: TRAIL/TRAIL Receptor System and Susceptibility to Multiple Sclerosis
Authors: López Gómez, Carlos
Fernández, Oscar
García León, Juan Antonio
Pinto Medel, María Jesús
Oliver Martos, Begoña
Ortega Pinazo, Jesús
Suardíaz, Margarita
García Trujillo, Lucía
Guijarro Castro, Cristina
Benito León, Julián
Prat, Isidro
Varadé, Jezabel
Álvarez-Lafuente, Roberto
Urcelay, Elena
Leyva, Laura
metadata.dc.contributor.authoraffiliation: [López,C; García,JA; Pinto,MJ; Oliver,B; Ortega,J; Suardíaz,M; Leyva,L] Research Laboratory, Clinical Neurosciences Institute, Hospital Universitario Carlos Haya and Fundación IMABIS, Málaga, Spain. [Fernández,O] Departament of Neurology, Clinical Neurosciences Institute, Hospital Regional Universitario Carlos Haya and Fundación IMABIS, Málaga, Spain. [Guijarro,C; Benito,J] Departament of Neurology, University Hospital 12 de Octubre, Madrid, Spain. [Benito,J] Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Madrid. Spain. Department of Medicine, Complutense University, Madrid, Spain. [Prat,I] Transfusion Center Blood Bank, Málaga, Spain. [Varadé,J; Urcelay,E] Department of Immunology, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria San Carlos (IdISSC), Madrid, Spain. [Álvarez,R] Department of Neurology, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria San Carlos (IdISSC), Madrid, Spain.
Keywords: Adolescente;Adulto;Anciano;Estudios de Casos y Controles;Estudios de Cohortes;Susceptibilidad a Enfermedades;Femenino;Genotipo;Humanos;Masculino;Mediana Edad;Multiple Esclerosis;Polimorfismo de Nucleótido Simple;Receptores del Ligando Inductor de Apoptosis Relacionado con TNF;Ligando Inductor de Apoptosis Relacionado con TNF;España;Adulto Joven
metadata.dc.subject.mesh: 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::Polymorphism, Single Nucleotide
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, Death Domain::Receptors, TNF-Related Apoptosis-Inducing Ligand
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intercellular Signaling Peptides and Proteins::Cytokines::Tumor Necrosis Factors::TNF-Related Apoptosis-Inducing Ligand
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genotype
Medical Subject Headings::Named Groups::Persons::Age Groups::Adolescent
Medical Subject Headings::Named Groups::Persons::Age Groups::Adult
Medical Subject Headings::Named Groups::Persons::Age Groups::Adult::Aged
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies
Medical Subject Headings::Phenomena and Processes::Physiological Phenomena::Body Constitution::Disease Susceptibility
Medical Subject Headings::Check Tags::Female
Medical Subject Headings::Check Tags::Male
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans
Medical Subject Headings::Named Groups::Persons::Age Groups::Adult::Middle Aged
Medical Subject Headings::Geographicals::Geographic Locations::Europe::Spain
Medical Subject Headings::Named Groups::Persons::Age Groups::Adult::Young Adult
Issue Date: 21-Jul-2011
Publisher: Public Library of Science
Citation: López-Gómez C, Fernández O, García-León JA, Pinto-Medel MJ, Oliver-Martos B, Ortega-Pinazo J, et al. TRAIL/TRAIL receptor system and susceptibility to multiple sclerosis. PLoS One. 2011;6(7):e21766
Abstract: The TNF-related apoptosis inducing ligand (TRAIL)/TRAIL receptor system participates in crucial steps in immune cell activation or differentiation. It is able to inhibit proliferation and activation of T cells and to induce apoptosis of neurons and oligodendrocytes, and seems to be implicated in autoimmune diseases. Thus, TRAIL and TRAIL receptor genes are potential candidates for involvement in susceptibility to multiple sclerosis (MS). To test whether single-nucleotide polymorphisms (SNPs) in the human genes encoding TRAIL, TRAILR-1, TRAILR-2, TRAILR-3 and TRAILR-4 are associated with MS susceptibility, we performed a candidate gene case-control study in the Spanish population. 59 SNPs in the TRAIL and TRAIL receptor genes were analysed in 628 MS patients and 660 controls, and validated in an additional cohort of 295 MS patients and 233 controls. Despite none of the SNPs withstood the highly conservative Bonferroni correction, three SNPs showing uncorrected p values<0.05 were successfully replicated: rs4894559 in TRAIL gene, p = 9.8×10(-4), OR = 1.34; rs4872077, in TRAILR-1 gene, p = 0.005, OR = 1.72; and rs1001793 in TRAILR-2 gene, p = 0.012, OR = 0.84. The combination of the alleles G/T/A in these SNPs appears to be associated with a reduced risk of developing MS (p = 2.12×10(-5), OR = 0.59). These results suggest that genes of the TRAIL/TRAIL receptor system exerts a genetic influence on MS.
Description: The authors acknowledge the support from Fondo de Investigación Sanitaria & Fondo Europeo de Desarrollo Regional (PS09/01764) and Consejería de Salud de la Junta de Andalucía (SAS07/0231) to LL, and from Consejería de Innovación (P07-CTS-03223) to OF. The authors also thank the “Red Temática de Investigación Cooperativa Red Española de Esclerosis Múltiple REEM (RD07/0060/0019)” and Fundación Española de Esclerosis Múltiple (FEDEM). CLG is a holder of a fellowship from Consejería de Salud de la Junta de Andalucía (PI 0231-2007), MJPM is a holder of a FIS fellowship (PI 05/1878); JAGL and MS are holders of fellowships from Consejería de Innovación de la Junta de Andalucía (P07-0223).
URI: http://hdl.handle.net/10668/489
metadata.dc.relation.publisherversion: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0021766
metadata.dc.identifier.doi: 10.1371/journal.pone.0021766
ISSN: 1932-6203 (Online)
Appears in Collections:01- Artículos - Hospital Regional de Málaga
01- Artículos - IBIMA. Instituto de Investigación Biomédica de Málaga

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