Genetic effects on age-dependent onset and islet cell autoantibody markers in type 1 diabetes.
2002 (English)In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 51, no 5, 1346-55 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2002. Vol. 51, no 5, 1346-55 p.
IdentifiersURN: urn:nbn:se:umu:diva-45404PubMedID: 11978629OAI: oai:DiVA.org:umu-45404DiVA: diva2:429382