In 2005, the interleukin 2 receptor alpha (IL2RA) region on chromosome 10p15 was found to be associated with type 1 diabetes. IL2RA encodes the α-chain of the IL-2 receptor complex (also referred to as CD25), which is responsible for binding IL-2, a key player in the proliferation of regulatory T cells. IL2R has also been associated with diabetes in the non-obese diabetic (NOD) mouse. Two IL2R SNPs associated with the increased risk of type 1 diabetes have been reported, with ss52580101 the most closely associated. A recent study measuring expression of IL2R in individuals homozygous for susceptible and protective SNPs associated with type 1 diabetes demonstrated that on stimulation, higher percentages of CD69+ CD4+ memory T cells secreted IL-2 from individuals with the protective SNP compared with individuals with the susceptible SNP. More recently susceptibility genotypes were found to be associated with lower levels of soluble IL2RA (sIL2RA) and in vitro stimulation of peripheral blood mononuclear cells from individuals with type 1 diabetes results in lower levels compared with healthy controls.


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