title: Insulin gene polymorphisms in type 1 diabetes, Addison's disease and the polyglandular autoimmune syndrome type II.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Internal Medicine I, Division of Endocrinology, Diabetes and Metabolism, University Hospital Frankfurt, Frankfurt am Main, Germany. elizabeth.ramos-lopez@kgu.de
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Ramos-Lopez
authors.forename: Britta
authors.initials: B
authors.lastname: Lange
authors.forename: Heinrich
authors.initials: H
authors.lastname: Kahles
authors.forename: Holger S
authors.initials: HS
authors.lastname: Willenberg
authors.forename: Gesine
authors.initials: G
authors.lastname: Meyer
authors.forename: Marissa
authors.initials: M
authors.lastname: Penna-Martinez
authors.forename: Nicole
authors.initials: N
authors.lastname: Reisch
authors.forename: Stefanie
authors.initials: S
authors.lastname: Hahner
authors.forename: Jürgen
authors.initials: J
authors.lastname: Seissler
authors.forename: Klaus
authors.initials: K
authors.lastname: Badenhoop
mesh_terms: D000224:Addison Disease / Q000150:complications / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000235:genetics*; D005838:Genotype; D006111:Graves Disease / Q000150:complications / Q000235:genetics; D050031:Hashimoto Disease / Q000150:complications / Q000235:genetics; D006801:Humans; D007223:Infant; D007328:Insulin / Q000235:genetics*; D008875:Middle Aged; D018598:Minisatellite Repeats; D016884:Polyendocrinopathies, Autoimmune / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic
chemical_list: D007328:Insulin