Abstract
Polymorphic variants at the interleukin-2 (IL2) locus affect the risk of several autoimmune disorders. Our aim was to evaluate the association of the four IL2 polymorphisms (rs6822844, rs6534349, rs2069762 and rs3136534) with type 1 diabetes (T1D) in the Polish population, and to correlate them with the serum interleukin-2 levels. 543 unrelated T1D patients and 706 healthy control subjects were enrolled. The minor T allele at rs6822844 was significantly less frequent in T1D compared to controls (p = 0.002; OR 0.71; 95 % CI 0.571–0.880). Likewise, the frequency of the TT genotype was decreased among the affected individuals (p = 0.007). In healthy subjects, stratification according to the rs6822844 genotype revealed significant differences in circulating interleukin-2 (p = 0.037) with the highest levels in TT protective genotypes. Three other IL2 polymorphisms did not display significant differences in allele and genotype distribution. In conclusion, the rs6822844 variant is associated with T1D and may play a functional role, or reflect the influence of another causative genetic variant in linkage disequilibrium.
Highlights
Type 1 diabetes (T1D) results from selective destruction of the insulin-secreting pancreatic beta cells by the autoreactive T lymphocytes
Our aim was to evaluate the association of the four IL2 polymorphisms with type 1 diabetes (T1D) in the Polish population, and to correlate them with the serum interleukin-2 levels. 543 unrelated T1D patients and 706 healthy control subjects were enrolled
Plausible association of the IL2 gene with diabetes was first suggested in non-obese diabetic (NOD) mouse model, based on congenic mapping of the Idd3 susceptibility locus [2]
Summary
Type 1 diabetes (T1D) results from selective destruction of the insulin-secreting pancreatic beta cells by the autoreactive T lymphocytes. To date several genetic loci have been identified which may affect the immune function and thereby contribute to T1D development. The strongest effect was demonstrated for the HLA region (chromosome 6p21), but other genes involved in the immune response play a role [1]. Functional data revealed that IL2 variants in NOD mice might affect the interleukin-2 production by antigen-specific T cells and predispose to organ-specific autoimmunity [3]. These analyses were followed by the first genome-wide association scan in human T1D, which showed a moderate evidence of the association with the IL2 region (4q27) [4]. Rs6534347, an intronic variant of the nearby KIAA1109 gene, was
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