RT Journal Article
T1 Candidate Gene Study of TRAIL and TRAIL Receptors: Association with Response to Interferon Beta Therapy in Multiple Sclerosis Patients
A1 López-Gómez, Carlos
A1 Pino-Ángeles, Almudena
A1 Órpez-Zafra, Teresa
A1 Pinto-Medel, Mª Jesús
A1 Oliver-Martos, Begoña
A1 Ortega-Pinazo, Jesús
A1 Arnáiz, Carlos
A1 Guijarro-Castro, Cristina
A1 Varadé, Jezabel
A1 Alvarez-Lafuente, Roberto
A1 Urcelay, Elena
A1 Sánchez-Jiménez, Francisca María
A1 Fernández Fernández, Oscar
A1 Leyva-Fernández, Laura
K1 Esclerosis múltiple - Tratamiento
AB TRAIL and TRAIL Receptor genes have been implicated in Multiple Sclerosis pathology as well as in the response to IFN betatherapy. The objective of our study was to evaluate the association of these genes in relation to the age at disease onset(AAO) and to the clinical response upon IFN beta treatment in Spanish MS patients. We carried out a candidate gene studyof TRAIL, TRAILR-1, TRAILR-2, TRAILR-3 and TRAILR-4 genes. A total of 54 SNPs were analysed in 509 MS patients under IFNbeta treatment, and an additional cohort of 226 MS patients was used to validate the results. Associations of rs1047275 inTRAILR-2 and rs7011559 in TRAILR-4 genes with AAO under an additive model did not withstand Bonferroni correction. Incontrast, patients with the TRAILR-1 rs20576-CC genotype showed a better clinical response to IFN beta therapy comparedwith patients carrying the A-allele (recessive model: p = 8.886 x 10-4, pc = 0.048, OR = 0.30). This SNP resulted in a nonsynonymous substitution of Glutamic acid to Alanine in position 228 (E228A), a change previously associated withsusceptibility to different cancer types and risk of metastases, suggesting a lack of functionality of TRAILR-1. In order tounravel how this amino acid change in TRAILR-1 would affect to death signal, we performed a molecular modelling withboth alleles. Neither TRAIL binding sites in the receptor nor the expression levels of TRAILR-1 in peripheral bloodmononuclear cell subsets (monocytes, CD4+ and CD8+ T cells) were modified, suggesting that this SNP may be altering thedeath signal by some other mechanism. These findings show a role for TRAILR-1 gene variations in the clinical outcome ofIFN beta therapy that might have relevance as a biomarker to predict the response to IFN beta in MS.
PB Public Library of Sciences
YR 2013
FD 2013
LK https://hdl.handle.net/10630/36810
UL https://hdl.handle.net/10630/36810
LA eng
NO López-Gómez C, Pino-Ángeles A, Órpez-Zafra T, Pinto-Medel MJ, Oliver-Martos B, Ortega-Pinazo J, Arnáiz C, Guijarro-Castro C, Varadé J, Álvarez-Lafuente R, Urcelay E, Sánchez-Jiménez F, Fernández Ó, Leyva L. Candidate gene study of TRAIL and TRAIL receptors: association with response to interferon beta therapy in multiple sclerosis patients. PLoS One.2013 Apr 29;8(4):e62540. doi: 10.1371/journal.pone.0062540. PMID: 23658636; PMCID: PMC3639207.
NO Artículo publicado PLoS One.2013 Apr 29;8(4):e62540
NO The authors acknowledge the support from Fondo de Investigacio´ n Sanitaria & Fondo Europeo de Desarrollo Regional (PS09/01764) and Consejerı´a deSalud de la Junta de Andalucı´a (SAS07/0231) to L.L., and from Consejerı´a de Innovacio´ n (P07-CTS-03223) to OF. The authors would like to thank Biogen Idec IberiaS.L. for financial support. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 3 mar 2026