Association of IL4 and IL4R polymorphisms with multiple sclerosis susceptibility in Caucasian population: A meta-analysis

J Neurol Sci. 2016 Apr 15:363:107-13. doi: 10.1016/j.jns.2016.02.049. Epub 2016 Feb 22.


Background: Previous studies have suggested a role for interleukin-4 (IL4) and its receptor (IL4R) gene in susceptibility to multiple sclerosis (MS), but the results remain controversial and under-powered.

Objectives: To investigate the contradictory results, we performed a meta-analysis to assess the possible association between polymorphisms of the IL4 rs2243250 (C/T), variable number of tandem repeat (VNTR) polymorphism in intron-3 (I3(709)VNTR), IL4R rs1801275 (T/C) and MS in Caucasian populations.

Methods: A comprehensive search was conducted to identify all case-control or cohort design studies. The fixed or random effect pooled measure was selected based on the homogeneity test among studies that was evaluated with I(2). Publication bias was estimated using the Begg's and Egger's test.

Results: A total of ten studies were included in the meta-analysis. The crude odds ratios (ORs) with 95% confidence intervals (95% CI) were calculated to evaluate the association. Overall, after excluding articles deviating from Hardy-Weinberg equilibrium in controls and sensitive analysis, the meta-analysis showed a significant association between polymorphism of IL4 rs2243250 and MS susceptibility in allele model (OR=1.209, 95% CI=1.022-1.429, P=0.026) and dominant model (OR =1.225, 95% CI=1.013-1.480, P=0.036). However, no significant association was found between polymorphisms of IL4 I3(709)*VNTR, IL4R rs1801275 and MS susceptibility, respectively.

Conclusions: The meta-analysis indicates that the T allele, CT and TT genotype of polymorphism of IL4 rs2243250 (C/T) may reduce the risk of MS in Caucasian populations, while polymorphisms of IL4 I3(709)*VNTR and IL4R rs1801275 may not associated with risk of MS in Caucasian populations.

Keywords: I3(709)*VNTR; IL4; Meta-analysis; Multiple sclerosis; rs1801275; rs2243250.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Case-Control Studies
  • Genetic Association Studies / methods
  • Genetic Predisposition to Disease / epidemiology
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Interleukin-4 / genetics*
  • Interleukin-4 Receptor alpha Subunit / genetics*
  • Multiple Sclerosis / diagnosis
  • Multiple Sclerosis / epidemiology
  • Multiple Sclerosis / genetics*
  • Population Surveillance / methods
  • White People / genetics*


  • IL4 protein, human
  • IL4R protein, human
  • Interleukin-4 Receptor alpha Subunit
  • Interleukin-4