CX3CR1 is a modifying gene of survival and progression in Amyotrophic Lateral Sclerosis

The objective of this study was to investigate the association of functional variants of the human CX3CR1 gene (Fractalkine receptor) with the risk of Amyotrophic Lateral Sclerosis disease (ALS), the survival and the progression rate of the disease symptoms in a Spanish ALS cohort. 187 ALS patients...

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Autores: López López, Alan, Gamez, Josep, Syriani, Emilio, Morales, Miguel, Salvado, Maria, Rodríguez Allué, Manuel José, Mahy Gehenne, Josette Nicole, Vidal Taboada, José Manuel
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2014
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/54704
Acceso en línea:https://hdl.handle.net/2445/54704
Access Level:acceso abierto
Palabra clave:Esclerosi lateral amiotròfica
Teràpia genètica
Malalties neurodegeneratives
Amyotrophic lateral sclerosis
Gene therapy
Neurodegenerative Diseases
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repository_id_str
spelling CX3CR1 is a modifying gene of survival and progression in Amyotrophic Lateral SclerosisLópez López, AlanGamez, JosepSyriani, EmilioMorales, MiguelSalvado, MariaRodríguez Allué, Manuel JoséMahy Gehenne, Josette NicoleVidal Taboada, José ManuelEsclerosi lateral amiotròficaTeràpia genèticaMalalties neurodegenerativesAmyotrophic lateral sclerosisGene therapyNeurodegenerative DiseasesThe objective of this study was to investigate the association of functional variants of the human CX3CR1 gene (Fractalkine receptor) with the risk of Amyotrophic Lateral Sclerosis disease (ALS), the survival and the progression rate of the disease symptoms in a Spanish ALS cohort. 187 ALS patients (142sporadic [sALS] and 45 familial) and 378 controls were recruited. We investigated CX3CR1 V249I (rs3732379) and T280M (rs3732378) genotypes and their haplotypes as predictors of survival, the progression rate of the symptoms (as measured by ALSFRS-R and FVC decline) and the risk of suffering ALS disease. The results indicated that sALS patients with CX3CR1 249I/I or 249V/I genotypes presented a shorter survival time (42.21±4.82) than patients with 249V/V genotype (67.48±7.28; diff=-25.27 months 95%CI [-42.09,-8.45]; p=0.003). The survival time was shorter in sALS patients with spinal topography and CX3CR1 249I alleles (diff -29.78 months; 95%CI [-49.42,-10.14]; p=0.003). The same effects were also observed in the spinal sALS patients with 249I-280M haplotype (diff=-27.23 months; 95%CI [-49.83,-4.64]; p=0.018). In the sALS group, the CX3CR1 249I variant was associated with a faster progression of the disease symptoms (OR= 2.32; 95IC%[1.24, 4.33]; p=0.007). There was no evidence for association of these two CX3CR1 variants with ALS disease risk. The association evidenced herein is clinically relevant and indicates that CX3CR1 could be a disease-modifying gene in sALS. The progression rate of the disease"s symptoms and the survival time is affected in patients with one or two copies of the CX3CR1 249I allele. The CX3CR1 is the most potent ALS survival genetic factor reported to date. These results reinforce the role of the immune system in ALS pathogenesis.Public Library of Science (PLoS)2014201420142014info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion8 p.application/pdfhttps://hdl.handle.net/2445/54704Articles publicats en revistes (Ciències Fisiològiques)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: http://dx.doi.org/10.1371/journal.pone.0096528PLoS One, 2014, vol. 9, num. 5, p. e96528http://dx.doi.org/10.1371/journal.pone.0096528cc-by (c) Lopez-Lopez, A. et al., 2014http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:recercat.cat:2445/547042026-05-29T05:05:01Z
dc.title.none.fl_str_mv CX3CR1 is a modifying gene of survival and progression in Amyotrophic Lateral Sclerosis
title CX3CR1 is a modifying gene of survival and progression in Amyotrophic Lateral Sclerosis
spellingShingle CX3CR1 is a modifying gene of survival and progression in Amyotrophic Lateral Sclerosis
López López, Alan
Esclerosi lateral amiotròfica
Teràpia genètica
Malalties neurodegeneratives
Amyotrophic lateral sclerosis
Gene therapy
Neurodegenerative Diseases
title_short CX3CR1 is a modifying gene of survival and progression in Amyotrophic Lateral Sclerosis
title_full CX3CR1 is a modifying gene of survival and progression in Amyotrophic Lateral Sclerosis
title_fullStr CX3CR1 is a modifying gene of survival and progression in Amyotrophic Lateral Sclerosis
title_full_unstemmed CX3CR1 is a modifying gene of survival and progression in Amyotrophic Lateral Sclerosis
title_sort CX3CR1 is a modifying gene of survival and progression in Amyotrophic Lateral Sclerosis
dc.creator.none.fl_str_mv López López, Alan
Gamez, Josep
Syriani, Emilio
Morales, Miguel
Salvado, Maria
Rodríguez Allué, Manuel José
Mahy Gehenne, Josette Nicole
Vidal Taboada, José Manuel
author López López, Alan
author_facet López López, Alan
Gamez, Josep
Syriani, Emilio
Morales, Miguel
Salvado, Maria
Rodríguez Allué, Manuel José
Mahy Gehenne, Josette Nicole
Vidal Taboada, José Manuel
author_role author
author2 Gamez, Josep
Syriani, Emilio
Morales, Miguel
Salvado, Maria
Rodríguez Allué, Manuel José
Mahy Gehenne, Josette Nicole
Vidal Taboada, José Manuel
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Esclerosi lateral amiotròfica
Teràpia genètica
Malalties neurodegeneratives
Amyotrophic lateral sclerosis
Gene therapy
Neurodegenerative Diseases
topic Esclerosi lateral amiotròfica
Teràpia genètica
Malalties neurodegeneratives
Amyotrophic lateral sclerosis
Gene therapy
Neurodegenerative Diseases
description The objective of this study was to investigate the association of functional variants of the human CX3CR1 gene (Fractalkine receptor) with the risk of Amyotrophic Lateral Sclerosis disease (ALS), the survival and the progression rate of the disease symptoms in a Spanish ALS cohort. 187 ALS patients (142sporadic [sALS] and 45 familial) and 378 controls were recruited. We investigated CX3CR1 V249I (rs3732379) and T280M (rs3732378) genotypes and their haplotypes as predictors of survival, the progression rate of the symptoms (as measured by ALSFRS-R and FVC decline) and the risk of suffering ALS disease. The results indicated that sALS patients with CX3CR1 249I/I or 249V/I genotypes presented a shorter survival time (42.21±4.82) than patients with 249V/V genotype (67.48±7.28; diff=-25.27 months 95%CI [-42.09,-8.45]; p=0.003). The survival time was shorter in sALS patients with spinal topography and CX3CR1 249I alleles (diff -29.78 months; 95%CI [-49.42,-10.14]; p=0.003). The same effects were also observed in the spinal sALS patients with 249I-280M haplotype (diff=-27.23 months; 95%CI [-49.83,-4.64]; p=0.018). In the sALS group, the CX3CR1 249I variant was associated with a faster progression of the disease symptoms (OR= 2.32; 95IC%[1.24, 4.33]; p=0.007). There was no evidence for association of these two CX3CR1 variants with ALS disease risk. The association evidenced herein is clinically relevant and indicates that CX3CR1 could be a disease-modifying gene in sALS. The progression rate of the disease"s symptoms and the survival time is affected in patients with one or two copies of the CX3CR1 249I allele. The CX3CR1 is the most potent ALS survival genetic factor reported to date. These results reinforce the role of the immune system in ALS pathogenesis.
publishDate 2014
dc.date.none.fl_str_mv 2014
2014
2014
2014
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/54704
url https://hdl.handle.net/2445/54704
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: http://dx.doi.org/10.1371/journal.pone.0096528
PLoS One, 2014, vol. 9, num. 5, p. e96528
http://dx.doi.org/10.1371/journal.pone.0096528
dc.rights.none.fl_str_mv cc-by (c) Lopez-Lopez, A. et al., 2014
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Lopez-Lopez, A. et al., 2014
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 8 p.
application/pdf
dc.publisher.none.fl_str_mv Public Library of Science (PLoS)
publisher.none.fl_str_mv Public Library of Science (PLoS)
dc.source.none.fl_str_mv Articles publicats en revistes (Ciències Fisiològiques)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,81155

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