Andrea Calvo1,2, Cristina Moglia1,2, Antonio Canosa1, Stefania Cammarosano1, Antonio Ilardi1, Davide Bertuzzo1, Bryan J Traynor3, Maura Brunetti1, Marco Barberis1, Gabriele Mora4, Federico Casale1, Adriano Chiò1,2,5. 1. "Rita Levi Montalcini" Department of Neuroscience, Neurology II, ALS Center, University of Torino, Via Cherasco 15, I-10126, Torino, Italy. 2. Azienda Ospedaliero-Universitaria Città della Salute e della Scienza, Torino, Italy. 3. Neuromuscular Diseases Research Section, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland, USA. 4. Salvatore Maugeri Foundation, IRCSS, Scientific Institute of Milano, Milano, Italy. 5. Institute of Cognitive Sciences and Technologies, National Council of Researches, Rome, Italy.
Abstract
INTRODUCTION: In the brain, the chemokine (C-X3-C motif) receptor 1 (1CX3CR1) gene is expressed only by microglia, where it acts as a key mediator of the neuron-microglia interactions. We assessed whether the 2 common polymorphisms of the CX3CR1 gene (V249I and T280M) modify amyotrophic lateral sclerosis (ALS) phenotype. METHODS: The study included 755 ALS patients diagnosed in Piemonte between 2007 and 2012 and 369 age-matched and sex-matched controls, all genotyped with the same chips. RESULTS: Neither of the variants was associated with an increased risk of ALS. Patients with the V249I V/V genotype had a 6-month-shorter survival than those with I/I or V/I genotypes (dominant model, P = 0.018). The T280M genotype showed a significant difference among the 3 genotypes (additive model, P = 0.036). Cox multivariable analysis confirmed these findings. DISCUSSION: We found that common variants of the CX3CR1 gene influence ALS survival. Our data provide further evidence for the role of neuroinflammation in ALS. Muscle Nerve 57: 212-216, 2018.
INTRODUCTION: In the brain, the chemokine (C-X3-C motif) receptor 1 (1CX3CR1) gene is expressed only by microglia, where it acts as a key mediator of the neuron-microglia interactions. We assessed whether the 2 common polymorphisms of the CX3CR1 gene (V249I and T280M) modify amyotrophic lateral sclerosis (ALS) phenotype. METHODS: The study included 755 ALSpatients diagnosed in Piemonte between 2007 and 2012 and 369 age-matched and sex-matched controls, all genotyped with the same chips. RESULTS: Neither of the variants was associated with an increased risk of ALS. Patients with the V249I V/V genotype had a 6-month-shorter survival than those with I/I or V/I genotypes (dominant model, P = 0.018). The T280M genotype showed a significant difference among the 3 genotypes (additive model, P = 0.036). Cox multivariable analysis confirmed these findings. DISCUSSION: We found that common variants of the CX3CR1 gene influence ALS survival. Our data provide further evidence for the role of neuroinflammation in ALS. Muscle Nerve 57: 212-216, 2018.
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