Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/54704
Title: CX3CR1 is a modifying gene of survival and progression in Amyotrophic Lateral Sclerosis
Author: Lopez-Lopez, Alan
Gamez, Josep
Syriani, Emilio
Morales, Miguel
Salvado, Maria
Rodríguez Allué, Manuel José
Mahy Gehenne, Josette Nicole
Vidal Taboada, José Manuel
Keywords: Esclerosi lateral amiotròfica
Teràpia genètica
Malalties neurodegeneratives
Amyotrophic lateral sclerosis
Gene therapy
Neurodegenerative Diseases
Issue Date: 7-May-2014
Publisher: Public Library of Science (PLoS)
Abstract: 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.
Note: Reproducció del document publicat a: http://dx.doi.org/10.1371/journal.pone.0096528
It is part of: PLoS One, 2014, vol. 9, num. 5, p. e96528
Related resource: http://dx.doi.org/10.1371/journal.pone.0096528
URI: http://hdl.handle.net/2445/54704
ISSN: 1932-6203
Appears in Collections:Articles publicats en revistes (Ciències Fisiològiques)

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