López Gómez, CarlosFernández, OscarGarcía León, Juan AntonioPinto Medel, María JesúsOliver Martos, BegoñaOrtega Pinazo, JesúsSuardíaz, MargaritaGarcía Trujillo, LucíaGuijarro Castro, CristinaBenito León, JuliánPrat, IsidroVaradé, JezabelÁlvarez-Lafuente, RobertoUrcelay, ElenaLeyva, Laura2012-09-262012-09-262011-07-21López-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):e21766http://hdl.handle.net/10668/489The 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).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.enAdolescenteAdultoAncianoEstudios de Casos y ControlesEstudios de CohortesSusceptibilidad a EnfermedadesFemeninoGenotipoHumanosMasculinoMediana EdadMultiple EsclerosisPolimorfismo de Nucleótido SimpleReceptores del Ligando Inductor de Apoptosis Relacionado con TNFLigando Inductor de Apoptosis Relacionado con TNFEspañaAdulto JovenMedical Subject Headings::Diseases::Immune System Diseases::Autoimmune Diseases::Autoimmune Diseases of the Nervous System::Demyelinating Autoimmune Diseases, CNS::Multiple SclerosisMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism, Genetic::Polymorphism, Single NucleotideMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, Death Domain::Receptors, TNF-Related Apoptosis-Inducing LigandMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intercellular Signaling Peptides and Proteins::Cytokines::Tumor Necrosis Factors::TNF-Related Apoptosis-Inducing LigandMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control StudiesMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::GenotypeMedical Subject Headings::Named Groups::Persons::Age Groups::AdolescentMedical Subject Headings::Named Groups::Persons::Age Groups::AdultMedical Subject Headings::Named Groups::Persons::Age Groups::Adult::AgedMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort StudiesMedical Subject Headings::Phenomena and Processes::Physiological Phenomena::Body Constitution::Disease SusceptibilityMedical Subject Headings::Check Tags::FemaleMedical Subject Headings::Check Tags::MaleMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Named Groups::Persons::Age Groups::Adult::Middle AgedMedical Subject Headings::Geographicals::Geographic Locations::Europe::SpainMedical Subject Headings::Named Groups::Persons::Age Groups::Adult::Young Adultresearch article21814551open access10.1371/journal.pone.00217661932-6203PMC3140982