Publication:
Candidate gene study of TRAIL and TRAIL receptors: association with response to interferon beta therapy in multiple sclerosis patients.

dc.contributor.authorLópez-Gómez, Carlos
dc.contributor.authorPino-Ángeles, Almudena
dc.contributor.authorÓrpez-Zafra, Teresa
dc.contributor.authorPinto-Medel, María Jesús
dc.contributor.authorOliver-Martos, Begoña
dc.contributor.authorOrtega-Pinazo, Jesús
dc.contributor.authorArnáiz, Carlos
dc.contributor.authorGuijarro-Castro, Cristina
dc.contributor.authorVaradé, Jezabel
dc.contributor.authorÁlvarez-Lafuente, Roberto
dc.contributor.authorUrcelay, Elena
dc.contributor.authorSánchez-Jiménez, Francisca
dc.contributor.authorFernández, Óscar
dc.contributor.authorLeyva, Laura
dc.contributor.authoraffiliation[López-Gomez,C; Órpez-ZafraT; Pinto-Medel,MJ; Oliver-Martos,B; Ortega-Pinazo,J; Leyva,L] Research Laboratory. Clinical Neurosciences Institute, Hospital Regional Universitario Carlos Haya, Málaga, Spain. [Pino-Ángeles,A; Sánchez-Jiménez,F] Department of Molecular Biology and Biochemistry, University of Málaga, Málaga, Spain. [Arnáiz,C; Fernández,O] Department of Neurology. Clinical Neurosciences Institute, Hospital Regional Universitario Carlos Haya, Málaga, Spain. [Guijarro-Castro,C] Department of Neurology, Hospital Universitario 12 de Octubre, Madrid, Spain. [Varadé,J; Álvarez-Lafuente,R; Urcelay,E] Multiple Sclerosis Unit, Hospital Clínico San Carlos, IdISSC, Madrid, Spain. [Pino-Ángeles,A; Sánchez-Jiménez,F] Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Málaga, Spain. [Órpez-Zafra,T; Pinto-Medel,MJ; Oliver-Martos,B; Guijarro-Castro,C; Varadé,J; Álvarez-Lafuente,R; Urcelay,E; Fernández,O; Leyva,L] Red Española de Esclerosis Múltiple (REEM RD 07/0060), Málaga, Spain.es
dc.contributor.funderFondo de Investigación Sanitaria & Fondo Europeo de Desarrollo Regional (PS09/01764), Consejería de Salud de la Junta de Andalucía (SAS07/0231), Consejería de Innovación (P07-CTS-03223) and Biogen Idec Iberia S.L.
dc.date.accessioned2013-10-17T10:51:05Z
dc.date.available2013-10-17T10:51:05Z
dc.date.issued2013-04-29
dc.descriptionJournal Article; Research Support, Non-U.S. Gov't;es
dc.description.abstractTRAIL and TRAIL Receptor genes have been implicated in Multiple Sclerosis pathology as well as in the response to IFN beta therapy. 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 study of TRAIL, TRAILR-1, TRAILR-2, TRAILR-3 and TRAILR-4 genes. A total of 54 SNPs were analysed in 509 MS patients under IFN beta treatment, and an additional cohort of 226 MS patients was used to validate the results. Associations of rs1047275 in TRAILR-2 and rs7011559 in TRAILR-4 genes with AAO under an additive model did not withstand Bonferroni correction. In contrast, patients with the TRAILR-1 rs20576-CC genotype showed a better clinical response to IFN beta therapy compared with patients carrying the A-allele (recessive model: p = 8.88×10(-4), pc = 0.048, OR = 0.30). This SNP resulted in a non synonymous substitution of Glutamic acid to Alanine in position 228 (E228A), a change previously associated with susceptibility to different cancer types and risk of metastases, suggesting a lack of functionality of TRAILR-1. In order to unravel how this amino acid change in TRAILR-1 would affect to death signal, we performed a molecular modelling with both alleles. Neither TRAIL binding sites in the receptor nor the expression levels of TRAILR-1 in peripheral blood mononuclear cell subsets (monocytes, CD4+ and CD8+ T cells) were modified, suggesting that this SNP may be altering the death signal by some other mechanism. These findings show a role for TRAILR-1 gene variations in the clinical outcome of IFN beta therapy that might have relevance as a biomarker to predict the response to IFN beta in MS.es
dc.description.versionYeses
dc.identifier.citationLópez-Gómez C, Pino-Ángeles A, Órpez-Zafra T, Pinto-Medel MJ, Oliver-Martos B, Ortega-Pinazo J, et al. Candidate gene study of TRAIL and TRAIL receptors: association with response to interferon beta therapy in multiple sclerosis patients. PLoS ONE. 2013; 8(4):e62540es
dc.identifier.doi10.1371/journal.pone.0062540
dc.identifier.essn1932-6203
dc.identifier.pmcPMC3639207
dc.identifier.pmid23658636
dc.identifier.urihttp://hdl.handle.net/10668/1330
dc.journal.titlePloS one
dc.language.isoen
dc.publisherPublic Library of Sciencees
dc.relation.publisherversionhttp://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0062540es
dc.rights.accessRightsopen access
dc.subjectEsclerosis múltiplees
dc.subjectEspañaes
dc.subjectGenotipoes
dc.subjectÁcido glutámicoes
dc.subjectAlaninaes
dc.subjectEdad de Inicioes
dc.subject.meshMedical Subject Headings::Diseases::Nervous System Diseases::Autoimmune Diseases of the Nervous System::Demyelinating Autoimmune Diseases, CNS::Multiple Sclerosises
dc.subject.meshMedical Subject Headings::Geographicals::Geographic Locations::Europe::Spaines
dc.subject.meshMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genotypees
dc.subject.meshMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Amino Acids::Amino Acids, Acidices
dc.subject.meshMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Amino Acids::Alaninees
dc.subject.meshMedical Subject Headings::Health Care::Environment and Public Health::Public Health::Epidemiologic Factors::Age Factors::Age of Onsetes
dc.titleCandidate gene study of TRAIL and TRAIL receptors: association with response to interferon beta therapy in multiple sclerosis patients.es
dc.typeresearch article
dc.type.hasVersionVoR
dspace.entity.typePublication
Files
Original bundle
Now showing 1 - 5 of 5
Loading...
Thumbnail Image
Name:
LopezGomezC_CandidateGeneStudy.pdf
Size:
2.59 MB
Format:
Adobe Portable Document Format
Description:
Artículo publicado
No Thumbnail Available
Name:
LopezGomezC_CandidateGene_TableS1.doc
Size:
136.5 KB
Format:
Microsoft Word
Description:
Supporting Information
No Thumbnail Available
Name:
LopezGomezC_CandidateGene_TableS2.doc
Size:
126.5 KB
Format:
Microsoft Word
Description:
Supporting Information
No Thumbnail Available
Name:
LopezGomezC_CandidateGene_TableS3.doc
Size:
28 KB
Format:
Microsoft Word
Description:
Supporting Information
No Thumbnail Available
Name:
LopezGomezC_CandidateGene_TableS4.doc
Size:
29.5 KB
Format:
Microsoft Word
Description:
Supporting Information