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.
Qu
Hui-Qi
HQ
Endocrine Genetics Laboratory, McGill University Health Center (Montréal Children's Hospital), Montréal, Québec, Canada.
Montpetit
Alexander
A
Ge
Bing
B
Hudson
Thomas J
TJ
Polychronakos
Constantin
C
D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology; D005060:Europe / Q000208:ethnology; D005091:Exons; D005260:Female; D005838:Genotype; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics*; D007438:Introns; D015810:Linkage Disequilibrium; D008297:Male; D009679:Nuclear Family; D020641:Polymorphism, Single Nucleotide; D013601:T-Lymphocytes / Q000276:immunology; D044465:White People
C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit