Expression of beta-cell autoimmunity does not differ between potential dizygotic twins and siblings of patients with type 1 diabetes Maria J. Redondo a , Pamela R. Fain a , Jeffrey P. Krischer b,c , Liping Yu a , David Cuthbertson b,c , William E. Winter d , George S. Eisenbarth a, * On behalf of the DPT-1 Study Group a Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, 4200 East Ninth Avenue B-140, Denver, CO 80262, United States b Department of Interdisciplinary Oncology, University of South Florida, Tampa, FL, United States c Department of Pediatrics, University of South Florida, Tampa, FL, United States d Department of Pathology, University of Florida, Gainesville, FL, United States Received 23 March 2004; revised 23 June 2004; accepted 12 July 2004 Abstract Twin studies help to elucidate the contribution of genes and environment to type 1 diabetes (T1DM). The Diabetes Prevention Trial-1 (DPT-1) tested for anti-islet autoantibodies: 34,765 non-diabetic non-twin siblings of patients with T1DM, and 896 non- diabetic potential twins of patients with T1DM. Zygosity (being monozygotic [MZ] or dizygotic [DZ]) was unknown except for 357 non-diabetic subjects with opposite gender to their diabetic twin, who must be DZ. Expression of cytoplasmic islet cell (ICA), GAD65, ICA512 and insulin autoantibodies in 357 different-sex (DZ) potential non-diabetic twins of T1DM patients was, respectively, 4.5%, 4.7%, 3.0% and 2.4%, which was lower than in 539 same-sex potential non-diabetic twins (including MZ and DZ) of T1DM patients for ICA (7.8%, p ! 0.05), GAD65 (13.4%, p ! 0.0001) and ICA512 (6.5%, p ! 0.03). In contrast, expression of ICA, GAD65, ICA512 and insulin autoantibodies was not significantly different in different-sex (DZ) potential twins versus all siblings (respectively, 4.2%, 4.8%, 2.2%, 2.5%), different-sex siblings (3.9%, 4.9%, 2.2%, 2.5%) or same-sex siblings (4.4%, 4.7%, 2.2%, 2.5%) of T1DM patients. In conclusion, anti-islet autoimmunity is not increased in non-diabetic DZ twins of T1DM patients compared to non-diabetic siblings of T1DM patients, suggesting that the greater environmental sharing by twins does not increase risk of anti-islet autoimmunity. Ó 2004 Elsevier Ltd. All rights reserved. Keywords: Environment; Genetics; Siblings; Twins; Type 1 diabetes 1. Introduction Twin studies have helped to define the importance of genetic and environmental factors in the etiology of disease [1e6]. Monozygotic (identical) twins (MZT) in- herit identical genes from their parents, while dizygotic (fraternal) twins (DZT) share, on average, half of their genetic material, as non-twin siblings do. Up to 50% of the MZT of patients with type 1 diabetes (T1DM) do not develop T1DM themselves despite long-term follow- up [7e10], suggesting both genetic and environmental factors are important in determining susceptibility to diabetes. Exposure to environmental factors, particu- larly intra-uterine and in early childhood, typically differs more between non-twin siblings than between twin mates. * Corresponding author. Tel.: C1 303 315 6165; fax: C1 303 315 4892. E-mail address: george.eisenbarth@uchsc.edu (G.S. Eisenbarth). 0896-8411/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.jaut.2004.07.001 Journal of Autoimmunity 23 (2004) 275e279 www.elsevier.com/locate/issn/08968411