Association of the interleukin-2 receptor alpha (IL-2Ralpha)/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 SC.
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-2Ralpha)/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 x 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.