The +190 G/A (rs1799864) polymorphism in the C-C chemokine receptor 2 (CCR2) gene is associated with susceptibility to multiple sclerosis in HLA-DRB1*15:01-negative individuals

J Neurol Sci. 2015 Feb 15;349(1-2):138-42. doi: 10.1016/j.jns.2015.01.002. Epub 2015 Jan 9.

Abstract

C-C chemokine receptor 2 (CCR2) is one of the key players involved in the transmigration of mononuclear cells into the central nervous system (CNS) and subsequent development of multiple sclerosis (MS). The aim of the current study was to analyse the association of CCR2 +190 G/A (rs1799864) polymorphism with susceptibility to MS and its influence on the age at onset, severity and neurological disability in MS. CCR2 genotyping was carried out by a polymerase chain reaction with restriction fragment length polymorphism (PCR-RFLP) in 301 MS patients and 342 healthy controls. Logistic regression analysis suggested a marginally significant association between MS and rs1799864 A allele (AA+GA vs. GG, P=0.047, OR=1.50, 95% CI=1.00-2.25), however, after stratification of study groups for the presence of HLA-DRB1*15:01 risk allele, this association could be found in HLA-DRB1*15:01-negative individuals only (AA+GA vs. GG, P=0.014, OR=1.84, 95% CI=1.13-2.98). Furthermore, there was no association between CCR2 polymorphism and clinical features of MS. In conclusion, our results suggest that CCR2 +190 G/A polymorphism may increase the susceptibility to MS, but its action seems to be restricted to individuals who do not possess the major risk allele HLA-DRB1*15:01.

Keywords: Association; CCR2; Chemokine; Multiple sclerosis; Single nucleotide polymorphism; Susceptibility.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age of Onset
  • Aged
  • Disease Susceptibility
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • HLA-DRB1 Chains / genetics*
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Multiple Sclerosis / diagnosis
  • Multiple Sclerosis / genetics*
  • Multiple Sclerosis / physiopathology
  • Polymorphism, Single Nucleotide*
  • Receptors, CCR2 / genetics*
  • Risk Factors
  • Young Adult

Substances

  • CCR2 protein, human
  • HLA-DRB1 Chains
  • Receptors, CCR2