Genetic effects on age-dependent onset and islet cell autoantibody markers in type 1 diabetes.

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Age-dependent associations between type 1 diabetes risk genes HLA, INS VNTR, and CTLA-4 and autoantibodies to GAD65 (GADAs), ICA512/IA-2, insulin, and islet cells were determined by logistic regression analysis in 971 incident patients with type 1 diabetes and 702 control subjects aged 0-34 years. GADAs were associated with HLA-DQ2 in young but not in older patients (P = 0.009). Autoantibodies to insulin were negatively associated with age (P < 0.0001) but positively associated with DQ8 (P = 0.03) and with INS VNTR (P = 0.04), supporting possible immune tolerance induction. ICA512/IA-2 were negatively associated with age (P < 0.0001) and with DQ2 (P < 0.0001) but positively associated with DQ8 (P = 0.04). Males were more likely than females to be negative for GADA (P < 0.0001), autoantibodies to islet cells (P = 0.04), and all four autoantibody markers (P = 0.004). The CTLA-4 3' end microsatellite marker was not associated with any of the autoantibodies. We conclude that age and genetic factors such as HLA-DQ and INS VNTR need to be combined with islet autoantibody markers when evaluating the risk for type 1 diabetes development.


  • J Graham
  • WA Hagopian
  • I Kockum
  • LS Li
  • CB Sanjeevi
  • RM Lowe
  • JB Schaefer
  • M Zarghami
  • HL Day
  • Mona Landin-Olsson
  • JP Palmer
  • M Janer-Villanueva
  • L Hood
  • G Sundkvist
  • Åke Lernmark
  • N Breslow
  • G Dahlquist
  • G Blohme
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Endocrinology and Diabetes
Original languageEnglish
Pages (from-to)1346-1355
Issue number5
Publication statusPublished - 2002
Publication categoryResearch