Toward Further Mapping of the Association Between the IL2RA Locus and Type 1 Diabetes
Open Access
- 1 April 2007
- journal article
- research article
- Published by American Diabetes Association in Diabetes
- Vol. 56 (4) , 1174-1176
- https://doi.org/10.2337/db06-1555
Abstract
A novel type 1 diabetes locus was mapped to the interleukin-2 receptor α 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 × 10−4 and 8.63 × 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, r2 = 0.613). The A-C haplotype (frequency = 0.331) was associated with increased type 1 diabetes risk (P = 3.02 × 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 IL2Rα in the pathogenesis of type 1 diabetes, likely involving regulatory T-cells.Keywords
This publication has 12 references indexed in Scilit:
- Structure of the Quaternary Complex of Interleukin-2 with Its α, ß, and γ c ReceptorsScience, 2005
- Type 1 DiabetesDiabetes, 2005
- Control of Type 1 Autoimmune Diabetes by Naturally Occurring CD4+CD25+Regulatory T Lymphocytes in Neonatal NOD MiceAnnals of the New York Academy of Sciences, 2005
- Localization of a Type 1 Diabetes Locus in the IL2RA/CD25 Region by Use of Tag Single-Nucleotide PolymorphismsAmerican Journal of Human Genetics, 2005
- Haploview: analysis and visualization of LD and haplotype mapsBioinformatics, 2004
- Meta-analysis of genetic association studies supports a contribution of common variants to susceptibility to common diseaseNature Genetics, 2003
- Certified ProfessionalsThe Journal of Experimental Medicine, 2001
- The family based association test method: strategies for studying general genotype–phenotype associationsEuropean Journal of Human Genetics, 2001
- Interleukin-2 receptor α chain regulates the size and content of the peripheral lymphoid compartmentImmunity, 1995
- Similarities between interleukin-2 receptor number and affinity on activated B and T lymphocytesNature, 1985