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

BMC Med Genet. 2008 Jul 11:9:65. doi: 10.1186/1471-2350-9-65.

Abstract

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 (T1D, 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 T1D and/or AD with HT or GD, n = 62) as well as in healthy controls (HC, n = 275).

Results: T1D 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 T1D but not to isolated AD, HT or as a part of the APS-II.

MeSH terms

  • Addison Disease / complications
  • Addison Disease / genetics*
  • Adolescent
  • Adult
  • Alleles
  • Case-Control Studies
  • Chi-Square Distribution
  • Child
  • Child, Preschool
  • Diabetes Mellitus, Type 1 / complications
  • Diabetes Mellitus, Type 1 / genetics*
  • Genotype
  • Graves Disease / complications
  • Graves Disease / genetics
  • Hashimoto Disease / complications
  • Hashimoto Disease / genetics
  • Humans
  • Infant
  • Insulin / genetics*
  • Middle Aged
  • Minisatellite Repeats
  • Polyendocrinopathies, Autoimmune / genetics*
  • Polymerase Chain Reaction
  • Polymorphism, Genetic*

Substances

  • Insulin