Insulin gene polymorphisms in type 1 diabetes, Addison's disease and the polyglandular autoimmune syndrome type II

Background: Polymorphisms within the insulin gene can influence insulin expression in the pancreas and especially in the thymus, where self-antigens are processed, shaping the T cell repertoire into selftolerance, a process that protects from beta-cell autoimmunity. Methods: We investigated the role of the -2221Msp(C/T) and -23HphI(A/T) polymorphisms within the insulin gene in patients with a monoglandular autoimmune endocrine disease [patients with isolated type 1 diabetes (TID, n = 317), Addison's disease ( AD, n = 107) or Hashimoto's thyroiditis ( HT, n = 61)], those with a polyglandular autoimmune syndrome type II ( combination of TID and/or AD with HT or GD, n = 62) as well as in healthy controls ( HC, n = 275). Results: TID patients carried significantly more often the homozygous genotype "CC" -2221Msp( C/T) and "AA" -23HphI(A/T) polymorphisms than the HC (78.5% vs. 66.2%, p = 0.0027 and 75.4% vs. 52.4%, p = 3.7 x 10(-8), respectively). The distribution of insulin gene polymorphisms did not show significant differences between patients with AD, HT, or APS-II and HC. Conclusion: We demonstrate that the allele "C" of the -2221Msp(C/T) and "A" -23HphI(A/T) insulin gene polymorphisms confer susceptibility to TID but not to isolated AD, HT or as a part of the APS-II.