Progression from islet autoimmunity to clinical type 1 diabetes is influenced by genetic factors: results from the prospective TEDDY study. Issue 9 (4th October 2018)

• Record Type: Journal Article
• Authors: Beyerlein, Andreas; Bonifacio, Ezio; Vehik, Kendra; Hippich, Markus; Winkler, Christiane; Frohnert, Brigitte I; Steck, Andrea K; Hagopian, William A; Krischer, Jeffrey P; Lernmark, Åke; Rewers, Marian J; She, Jin-Xiong; Toppari, Jorma; Akolkar, Beena; Rich, Stephen S; Ziegler, Anette-G
• Is Part Of: Journal of medical genetics. Volume 56:Issue 9(2019)
• Page Start: 602
• Page End: 605
• Publication Date: 2018-10-04
• Subjects: diabetes -- diagnostics tests -- epidemiology -- immunology (including allergy); Medical genetics -- Periodicals; 616.042
• DOI: 10.1136/jmedgenet-2018-105532
• Languages: English
• ISSNs: 1468-6244

Abstract

Abstract : Background: Progression time from islet autoimmunity to clinical type 1 diabetes is highly variable and the extent that genetic factors contribute is unknown. Methods: In 341 islet autoantibody-positive children with the human leucocyte antigen (HLA) DR3/DR4-DQ8 or the HLA DR4-DQ8/DR4-DQ8 genotype from the prospective TEDDY (The Environmental Determinants of Diabetes in the Young) study, we investigated whether a genetic risk score that had previously been shown to predict islet autoimmunity is also associated with disease progression. Results: Islet autoantibody-positive children with a genetic risk score in the lowest quartile had a slower progression from single to multiple autoantibodies (p=0.018), from single autoantibodies to diabetes (p=0.004), and by trend from multiple islet autoantibodies to diabetes (p=0.06). In a Cox proportional hazards analysis, faster progression was associated with an increased genetic risk score independently of HLA genotype (HR for progression from multiple autoantibodies to type 1 diabetes, 1.27, 95% CI 1.02 to 1.58 per unit increase), an earlier age of islet autoantibody development (HR, 0.68, 95% CI 0.58 to 0.81 per year increase in age) and female sex (HR, 1.94, 95% CI 1.28 to 2.93). Conclusions: Genetic risk scores may be used to identify islet autoantibody-positive children with high-risk HLA genotypes who have a slow rate of progression to subsequent stages of autoimmunity and type 1 diabetes.