Genetic determination of islet cell autoimmunity in monozygotic twin, dizygotic twin, and non-twin siblings of patients with type 1 diabetes: prospective twin study

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Abstract
Objective: To test the hypothesis that non-diabetic dizygotic and monozygotic twin siblings of patients with type 1 diabeteshave a similar high prevalence of islet cell autoantibodies, thus suggesting that islet cell autoimmunity is mainly environmentally determined. Design: Prospective twin study. Setting: Two specialist centres for diabetes in the United States. Participants: Non-diabetic monozygotic twin (n=53), dizygotic twin (n=30), and non-twin (n=149) siblings of patients with type 1 diabetes; 101 controls. Main outcome measures: Analysis of progression to diabetes and expression of anti-islet autoantibodies. Results: Monozygotic twin siblings had a higher risk of progression to diabetes (12/53) than dizygotic twin siblings (0/30; Pv 1/23; Pv 23.5% (7% to 40%) at 10 years of discordance; PConclusion: Monozygotic and dizygotic twins differ in progression to diabetes and expression of islet cell autoantibodies. Dizygotic twin siblings are similar to non-twin siblings. These two observations suggest that genetic factors play an important part in determination of islet cell autoimmunity, thus rejecting the hypothesis. In addition, there is a high penetrance of islet cell autoimmunity in DQ8/DQ2 monozygotic twin siblings.