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.
Highlights
Type 1 diabetes (T1D) is a complex, multigenetic autoimmune disease featured by destruction of the insulin producing beta-cells of the pancreas by autoreactive T lymphocytes
Any human genetic association study, regardless of sample size, was included in the meta-analysis if it met the following criteria: (i) study evaluated the association of interleukin 2 receptor alpha (IL2RA) polymorphisms with T1D; (ii) study had sufficient published data to estimate an odds ratio (OR) with 95% confidence interval (CI) or provided raw data that allowed us to calculate them; (iii) if the data were duplicated or had been published more than once, the most recent and complete study was chosen; (iv) studies were excluded if the genotype distribution of the controls deviated from Hardy-Weinberg equilibrium (HWE) and (v) review articles, abstracts, editorials, reports with incomplete data and studies based on pedigree data were excluded
Several genome-wide association studies (GWAS) and a number of case-control studies have examined the association between the investigated five single nucleotide polymorphism (SNP) and T1D risk, but the results showed significant between-study variation
Summary
Type 1 diabetes (T1D) is a complex, multigenetic autoimmune disease featured by destruction of the insulin producing beta-cells of the pancreas by autoreactive T lymphocytes. Five common tag SNPs were mainly observed, which had no obvious linkage disequilibrium to each other [5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21]. These are two intronic SNPs in the 50 region of IL2RA, rs706778 and rs3118470; two SNPs mapping to the 50 flanking region, rs41295061 (previously named ss52580101 or rs12722495) and rs11594656; and one SNP in the intron 1, rs2104286. It has been demonstrated that rs41295061 was associated with glutamate decarboxylase antibody positivity in T1D patients [22], and Lowe et al [5] found that rs11594656, rs2104286 and rs41295061 independently correlated with the circulating concentration of a 2015 The Authors
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