Common polymorphisms of chemokine (C-X3-C motif) receptor 1 gene modify amyotrophic lateral sclerosis outcome: A population-based study.
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.



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.



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.



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.
"Rita Levi Montalcini" Department of Neuroscience, Neurology II, ALS Center, University of Torino, Via Cherasco 15, I-10126, Torino, Italy.|Azienda Ospedaliero-Universitaria Città della Salute e della Scienza, Torino, Italy.
Andrea
A
Calvo
"Rita Levi Montalcini" Department of Neuroscience, Neurology II, ALS Center, University of Torino, Via Cherasco 15, I-10126, Torino, Italy.|Azienda Ospedaliero-Universitaria Città della Salute e della Scienza, Torino, Italy.
Cristina
C
Moglia
"Rita Levi Montalcini" Department of Neuroscience, Neurology II, ALS Center, University of Torino, Via Cherasco 15, I-10126, Torino, Italy.
Antonio
A
Canosa
"Rita Levi Montalcini" Department of Neuroscience, Neurology II, ALS Center, University of Torino, Via Cherasco 15, I-10126, Torino, Italy.
Stefania
S
Cammarosano
"Rita Levi Montalcini" Department of Neuroscience, Neurology II, ALS Center, University of Torino, Via Cherasco 15, I-10126, Torino, Italy.
Antonio
A
Ilardi
"Rita Levi Montalcini" Department of Neuroscience, Neurology II, ALS Center, University of Torino, Via Cherasco 15, I-10126, Torino, Italy.
Davide
D
Bertuzzo
Neuromuscular Diseases Research Section, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland, USA.
Bryan J
BJ
Traynor
"Rita Levi Montalcini" Department of Neuroscience, Neurology II, ALS Center, University of Torino, Via Cherasco 15, I-10126, Torino, Italy.
Maura
M
Brunetti
"Rita Levi Montalcini" Department of Neuroscience, Neurology II, ALS Center, University of Torino, Via Cherasco 15, I-10126, Torino, Italy.
Marco
M
Barberis
Salvatore Maugeri Foundation, IRCSS, Scientific Institute of Milano, Milano, Italy.
Gabriele
G
Mora
"Rita Levi Montalcini" Department of Neuroscience, Neurology II, ALS Center, University of Torino, Via Cherasco 15, I-10126, Torino, Italy.
Federico
F
Casale
"Rita Levi Montalcini" Department of Neuroscience, Neurology II, ALS Center, University of Torino, Via Cherasco 15, I-10126, Torino, Italy.|Azienda Ospedaliero-Universitaria Città della Salute e della Scienza, Torino, Italy.|Institute of Cognitive Sciences and Technologies, National Council of Researches, Rome, Italy.
Adriano
A
Chiò
D017668:Age of Onset; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000473:pathology; D000073883:CX3C Chemokine Receptor 1 / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007249:Inflammation / Q000473:pathology; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D011153:Population; D040081:Protein Array Analysis; D016019:Survival Analysis
D000073883:CX3C Chemokine Receptor 1; C095235:CX3CR1 protein, human
CX3CR1 gene; amyotrophic lateral sclerosis; microglia; neurodegeneration; survival