CX3CR1 is a modifying gene of survival and progression in Amyotrophic Lateral Sclerosis
| Autor: | López López, Alan, Gamez, Josep, Syriani, Emilio, Morales, Miguel, Salvado, Maria, Rodríguez Allué, Manuel José, Mahy Gehenne, Josette Nicole, Vidal Taboada, José Manuel |
|---|---|
| Přispěvatelé: | Universitat de Barcelona |
| Předmět: |
Adult
Male Heredity Clinical Pathology Genotype Clinical Research Design CX3C Chemokine Receptor 1 lcsh:Medicine Pathology and Laboratory Medicine Research and Analysis Methods Polymorphism Single Nucleotide Molecular Genetics Motor Neuron Diseases Cohort Studies Gene therapy Diagnostic Medicine Genetics Medicine and Health Sciences Humans Genetic Predisposition to Disease lcsh:Science Alleles Aged Aged 80 and over Evolutionary Biology Population Biology Amyotrophic Lateral Sclerosis lcsh:R Malalties neurodegeneratives Neurodegenerative diseases Biology and Life Sciences Neurodegenerative Diseases Middle Aged Amyotrophic lateral sclerosis Survival Rate Haplotypes Neurology Spain Research Design Genetics of Disease Disease Progression Teràpia genètica Female Receptors Chemokine lcsh:Q Population Genetics Esclerosi lateral amiotròfica Research Article |
| Zdroj: | Recercat. Dipósit de la Recerca de Catalunya instname PLoS ONE, Vol 9, Iss 5, p e96528 (2014) PLoS ONE Dipòsit Digital de la UB Universidad de Barcelona |
| Popis: | 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 249I/I or 249V/I genotypes presented a shorter survival time (42.27 ± 4.90) than patients with 249V/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 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 = -27.02 months; 95%CI [-49.57, -4.48]; p = 0.019). In the sALS group, the CX3CR1 249I 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|