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, Laura2024-01-152024-01-152011-07-21http://hdl.handle.net/10668/489http://hdl.handle.net/20.500.12105/17028The 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.engVoRhttps://creativecommons.org/licenses/by/4.0/AdolescenteAdultoAncianoEstudios 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 JovenMultiple SclerosisPolymorphism, Single NucleotideReceptors, TNF-Related Apoptosis-Inducing LigandTNF-Related Apoptosis-Inducing LigandCase-Control StudiesGenotypeAdolescentAdultAgedCohort StudiesMaleHumansMiddle AgedSpainYoung AdultAttribution 4.0 International2181455110.1371/journal.pone.00217661932-6203PLoS ONEopen access