Association between IL2/IL21 and SH2B3 polymorphisms and risk of celiac disease: a meta-analysis

Genet Mol Res. 2015 Oct 27;14(4):13221-35. doi: 10.4238/2015.October.26.19.

Abstract

Celiac disease (CD) is a common autoimmune disorder characterized by heightened immunological response to ingested gluten. Certain gene polymorphisms of IL2/IL21 (rs6822844 and rs6840978) and SH2B3 (rs3184504) may influence susceptibility to CD, although the effects remain unclear. We performed a meta-analysis of the associations between rs6822844, rs6840978, and rs3184504 polymorphisms and CD risk. PubMed, EMBASE, and the China National Knowledge Infrastructure were searched. ORs and 95%CIs of each single nucleotide polymorphism (SNP) were estimated using the fixed-effect model if I(2) < 50% in the test of heterogeneity; otherwise, the random-effect model was used. Our meta-analysis included 12,986 CD cases and 28,733 controls from 16 independent samples, and the analysis of each SNP contained a subset of the total. We found that the minor allele T of both rs6822844 (T vs G, OR = 0.72, 95%CI = 0.67-0.78, P < 0.001) and rs6840978 (T vs C, OR = 0.76, 95%CI = 0.71-0.83, P < 0.001) in IL2/IL21 significantly decreased the risk of CD. However, the minor allele A of rs3184504 (A vs G, OR = 1.18, 95%CI = 1.12-1.24, P < 0.001) in SH2B3 significantly increased CD susceptibility. The estimated lambda values were 0.49, 0.50, and 0.53 for rs6822844, rs6840978, and rs3184504, respectively, suggesting that a co-dominant model of genotype effect was most appropriate for the three SNPs. Our results support associations between the three SNPs and CD and provide a strong argument for further research.

Publication types

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

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Alleles
  • Case-Control Studies
  • Celiac Disease / epidemiology
  • Celiac Disease / genetics*
  • Gene Frequency
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • Interleukin-2 / genetics*
  • Interleukins / genetics*
  • Intracellular Signaling Peptides and Proteins
  • Odds Ratio
  • Polymorphism, Single Nucleotide*
  • Proteins / genetics*
  • Publication Bias
  • Risk

Substances

  • Adaptor Proteins, Signal Transducing
  • Interleukin-2
  • Interleukins
  • Intracellular Signaling Peptides and Proteins
  • Proteins
  • SH2B3 protein, human
  • interleukin-21