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

Muscle Nerve. 2018 Feb;57(2):212-216. doi: 10.1002/mus.25653. Epub 2017 Apr 25.

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.

Keywords: CX3CR1 gene; amyotrophic lateral sclerosis; microglia; neurodegeneration; survival.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age of Onset
  • Aged
  • Amyotrophic Lateral Sclerosis / genetics*
  • Amyotrophic Lateral Sclerosis / pathology
  • CX3C Chemokine Receptor 1 / genetics*
  • Female
  • Genetic Variation
  • Genotype
  • Humans
  • Inflammation / pathology
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Polymorphism, Genetic / genetics
  • Population
  • Protein Array Analysis
  • Survival Analysis

Substances

  • CX3C Chemokine Receptor 1
  • CX3CR1 protein, human