CX3CR1 Is a Modifying Gene of Survival and Progression in Amyotrophic Lateral Sclerosis
Lopez-Lopez, Alan (Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas)
Gamez, Josep (Hospital Universitari Vall d'Hebron)
Syriani, Emilio (Hospital Universitari Vall d'Hebron)
Morales, Miguel (Synaptic Structural Plasticity Lab (Logroño))
Salvado, Maria (Hospital Universitari Vall d'Hebron)
Rodríguez, Manuel J. (Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas)
Mahy, Nicole (Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas)
Vidal-Taboada, Jose M. (Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas)
Universitat Autònoma de Barcelona

Date:	2014
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 (ALS), the survival and the progression rate of the disease symptoms in a Spanish ALS cohort. 187 ALS patients (142 sporadic [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 249 I/I or 249 V/I genotypes presented a shorter survival time (42. 27±4. 90) than patients with 249 V/V genotype (67. 65±7. 42; diff -25. 49 months 95%CI [-42. 79,-8. 18]; p = 0. 004; adj-p = 0. 018). The survival time was shorter in sALS patients with spinal topography and CX3CR1 249 I 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 249 I -280 M haplotype (diff = -27. 02 months; 95%CI [-49. 57, -4. 48]; p = 0. 019). In the sALS group, the CX3CR1 249 I variant was associated with a faster progression of the disease symptoms (OR = 2. 58; 95IC% [1. 32, 5. 07]; p = 0. 006; adj-p = 0. 027). 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.
Grants:	Ministerio de Ciencia e Innovación SAF2008-01902 Ministerio de Ciencia e Innovación IPT-010000-2010-35 Ministerio de Economía y Competitividad PI13-01272
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	PloS one, Vol. 9 (may 2014) , ISSN 1932-6203

DOI: 10.1371/journal.pone.0096528
PMID: 24806473

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