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

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.

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@article{Graham2002GeneticEO, title={Genetic effects on age-dependent onset and islet cell autoantibody markers in type 1 diabetes.}, author={Jinko Graham and William A Hagopian and Ingrid Kockum and Lou Sheng Li and Carani B Sanjeevi and Robert M Lowe and Jonathan B Schaefer and Marjan Zarghami and Heather L Day and Mona Landin-Olsson and Jerry P Palmer and Marta Janer-Villanueva and Leroy Hood and G{\"{o}ran Sundkvist and Ake Lernmark and Norman Breslow and Gisela Dahlquist and G{\"{o}ran Blohm{\'e}}, journal={Diabetes}, year={2002}, volume={51 5}, pages={1346-55} }