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

Diabetes. 2002 May;51(5):1346-55. doi: 10.2337/diabetes.51.5.1346.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Autoantibodies / blood*
  • Biomarkers
  • Child
  • Child, Preschool
  • Diabetes Mellitus, Type 1 / epidemiology*
  • Diabetes Mellitus, Type 1 / genetics*
  • Diabetes Mellitus, Type 1 / immunology
  • Female
  • Genotype
  • HLA-DQ Antigens / genetics
  • Humans
  • Infant
  • Infant, Newborn
  • Islets of Langerhans / immunology*
  • Logistic Models
  • Male
  • Risk Factors
  • Seroepidemiologic Studies
  • Sex Distribution

Substances

  • Autoantibodies
  • Biomarkers
  • HLA-DQ Antigens
  • HLA-DQ2 antigen
  • HLA-DQ8 antigen