Toward further mapping of the association between the IL2RA locus and type 1 diabetes.

A novel type 1 diabetes locus was mapped to the interleukin-2 receptor alpha gene (IL2RA) on chromosome 10p15.1, encoding an important modulator of immunity. The aim of the current study was to confirm the association of IL2RA with type 1 diabetes and to attempt further mapping of the genetic effect with a new set of 12 single nucleotide polymorphisms (SNPs). We genotyped 949 nuclear family trios with one type 1 diabetes-affected offspring and two parents (2,847 individuals). Two of the 12 IL2RA SNPs genotyped (rs706778 and rs3118470) had statistically significant type 1 diabetes association (P = 6.96 x 10(-4) and 8.63 x 10(-4), respectively). Both SNPs are located in the 5' end of the long intron 1 within 3 kb of each other and are in high linkage disequilibrium (D' = 0.997, r(2) = 0.613). The A-C haplotype (frequency = 0.331) was associated with increased type 1 diabetes risk (P = 3.02 x 10(-4)). Our study identifies two markers in the IL2RA gene that are significantly associated with type 1 diabetes, supporting IL2RA as a promising candidate gene for type 1 diabetes and suggesting a potential role of IL2Ralpha in the pathogenesis of type 1 diabetes, likely involving regulatory T-cells.