Association of common polymorphisms in the IL2RA gene with type 1 diabetes: evidence of 32,646 individuals from 10 independent studies

J Cell Mol Med. 2015 Oct;19(10):2481-8. doi: 10.1111/jcmm.12642. Epub 2015 Aug 7.

Abstract

Single nucleotide polymorphisms (SNPs) in the interleukin 2 receptor alpha (IL2RA) gene have been suggested to be associated with type 1 diabetes (T1D) susceptibility. However, the results from individual studies are inconsistent. To explore the association of IL2RA polymorphisms with T1D, including rs11594656, rs2104286, rs3118470, rs41295061 and rs706778, a meta-analysis involving 10 independent studies with 19 outcomes was conducted: five studies with a total of 10,572 cases and 12,956 controls were analysed for rs11594656 with T1D risk, three studies with 7300 cases and 8331 controls for rs2104286, three studies with 3880 cases and 5409 controls for rs3118470, five studies with 11,253 cases and 13,834 controls for rs41295061 and three studies with 1896 cases and 1709 controls for rs706778 respectively. Using minor allelic comparison, the five investigated SNPs were all observed to have a significant association with T1D: For rs11594656, fixed effect model (FEM) odds ratio (OR) 0.87, 95% confidence interval (CI) 0.83, 0.91; rs2104286, FEM OR 0.81, 95% CI 0.77, 0.85; rs3118470, FEM OR 1.23, 95% CI 1.16, 1.31; rs41295061, random effect model (REM) OR 0.67, 95% CI 0.60, 0.76 and rs706778 FEM OR 1.20, 95% CI 1.08, 1.33. Similar results were obtained when all the included studies were calculated by a REM. Our meta-analysis suggests that all five SNPs in the IL2RA gene are risk factors for T1D risk, and rs11594656, rs2104286 and rs41295061 are the most associated SNPs in the populations investigated. This conclusion warrants confirmation by further studies.

Keywords: interleukin 2 receptor alpha; meta-analysis; single nucleotide polymorphism; type 1 diabetes.

Publication types

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

MeSH terms

  • Alleles
  • Diabetes Mellitus, Type 1 / genetics*
  • Genetic Association Studies*
  • Genetic Heterogeneity
  • Genetic Predisposition to Disease*
  • Humans
  • Interleukin-2 Receptor alpha Subunit / genetics*
  • Odds Ratio
  • Polymorphism, Single Nucleotide / genetics*
  • Publication Bias
  • Risk Factors

Substances

  • Interleukin-2 Receptor alpha Subunit