Genetic Associations of Interleukin-related Genes with Graves' Ophthalmopathy: a Systematic Review and Meta-analysis

Sci Rep. 2015 Nov 18:5:16672. doi: 10.1038/srep16672.

Abstract

Graves' ophthalmopathy (GO) is the commonest extra-thyroidal manifestation of Graves' disease (GD). Associations between interleukin-related (IL) gene polymorphisms and GO have been reported in different populations. We aim to confirm such associations by conducting a meta-analysis. Totally 382 publications were retrieved in MEDLINE and EMBASE up to 25/2/2015. After removing the duplicates and assessing the studies, we retrieved 16 studies that met the selection criteria for meta-analysis, involving 12 polymorphisms in 8 IL-related genes, and 1650 GO cases and 2909 GD controls. The summary odds ratio (OR) and 95% confidence intervals (CI) were estimated. We found one polymorphism in IL1A (rs1800587, c.-889C>T) showing a suggestive association with GO in the meta-analysis (allelic model [T vs. C]: OR = 1.62, 95% CI: 1.00-2.62, P = 0.050, I(2) = 53.7%; recessive model [TT vs. TC + CC]: OR = 2.39, 95% CI: 1.07-5.37, P = 0.039, I(2) = 23.6%; heterozygous model [TC vs. CC]: OR = 1.52, 95% CI: 1.04-2.22, P = 0.034, I(2) = 37.0%). No association with GO was detected for the other 7 genes (IL1B, IL1RA, IL4, IL6, IL12B, IL13 and IL23R). Our results thus indicate that IL1A is likely to be a genetic biomarker for GO. Further studies with larger sample sizes are warranted to confirm the associations of IL1A and other IL-related genes with GO.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Alleles
  • Gene Frequency
  • Genetic Association Studies*
  • Genetic Predisposition to Disease*
  • Genotype
  • Graves Ophthalmopathy / genetics*
  • Humans
  • Interleukins / genetics*
  • Odds Ratio
  • Polymorphism, Single Nucleotide
  • Publication Bias

Substances

  • Interleukins