Association of the interleukin-2 receptor alpha (IL-2Rα)/CD25 gene region with Graves’ disease using a multilocus test and tag SNPs
Brand OJ., Lowe CE., Heward JM., Franklyn JA., Cooper JD., Todd JA., Gough SCL.
Objective: A small number of immune response genes have been consistently associated with the common autoimmune conditions. Recently, a linkage disequilibrium (LD) mapping approach, using tag single nucleotide polymorphisms (SNPs), identified genetic association between type 1 diabetes (T1D) and the interleukin-2 receptor alpha (IL-2Rα)/CD25 gene region on chromosome 10p15. Because certain autoimmune diseases, such as autoimmune thyroid disease (AITD) and T1D cluster together in certain families, we sought to determine if the TID-associated CD25 region was also associated with Graves’ disease (GD). Design: We performed a case-control association study of 20 tag SNPs. Patients: 1896 GD patients were collected from seven major centres in the UK and 1822 geographically matched controls from the 1958 British Birth Cohort. Measurements: The 20 tag SNPs were analysed using a multilocus test to identify an association between GD and the CD25 region. Odds ratios (ORs) were calculated for the tag SNPs, allowing a comparison with previous results for T1D. Results: The multilocus test provided statistical evidence of an association between GD and the CD25 region (P = 4.5 × 10-4), with the pattern of association of the 20 tag SNPs similar to that found in T1D. Conclusions: Association with GD, as well as that previously reported with T1D, suggests that the CD25 region is acting as a general susceptibility locus for autoimmune disease, and is consistent with a major role for the IL-2-receptor pathway in the development and function of T cells in the control of autoimmunity. © 2007 The Authors.