title: TRAIL/TRAIL receptor system and susceptibility to multiple sclerosis.
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.
authors.affiliation: Research Laboratory, Clinical Neurosciences Institute, Hospital Regional Universitario Carlos Haya and Fundación IMABIS, Málaga, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: López-Gómez
authors.forename: Oscar
authors.initials: O
authors.lastname: Fernández
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: García-León
authors.forename: María Jesús
authors.initials: MJ
authors.lastname: Pinto-Medel
authors.forename: Begoña
authors.initials: B
authors.lastname: Oliver-Martos
authors.forename: Jesús
authors.initials: J
authors.lastname: Ortega-Pinazo
authors.forename: Margarita
authors.initials: M
authors.lastname: Suardíaz
authors.forename: Lucía
authors.initials: L
authors.lastname: García-Trujillo
authors.forename: Cristina
authors.initials: C
authors.lastname: Guijarro-Castro
authors.forename: Julián
authors.initials: J
authors.lastname: Benito-León
authors.forename: Isidro
authors.initials: I
authors.lastname: Prat
authors.forename: Jezabel
authors.initials: J
authors.lastname: Varadé
authors.forename: Roberto
authors.initials: R
authors.lastname: Álvarez-Lafuente
authors.forename: Elena
authors.initials: E
authors.lastname: Urcelay
authors.forename: Laura
authors.initials: L
authors.lastname: Leyva
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D015331:Cohort Studies; D004198:Disease Susceptibility; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics*; D013030:Spain; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics*; D055815:Young Adult
chemical_list: D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand