Emerging effects of early environmental factors over genetic background for type 1 diabetes susceptibility: Evidence from a nationwide Italian twin study

Lorenza Nisticò, Dario Iafusco, Alfonso Galderisi, Corrado Fagnani, Rodolfo Cotichini, Virgilia Toccaceli, Maria Antonietta Stazi, Valentino Cherubini, Antonio Iannilli, Anna Maria Paparusso, Luciano Cavallo, Clara Zecchino, Gianpaolo De Filippo, Luigi Gargantini, Silvana Salardi, Stefano Zucchini, Giulio Maltoni, Bruno Pasquino, Peter Kaufmann, Fabio BuziElena Prandi, Francesco Gallo, Mario Cicchetti, Enzo Castaldo, Felice Citriniti, Franco Chiarelli, Stefano Tumini, Alessia Di Stefano, Domenico Sperlì, Rosaria De Marco, Patrizia Banin, Sonia Toni, Lorenzo Lenzi, Maurizio Del Vecchio, Renata Lorini, Giuseppe D'Annunzio, Dario Ingletto, Andrea Scaramuzza, Gian Vincenzo Zuccotti, Giuseppe Chiumello, Franco Meschi, Riccardo Bonfanti, Giulio Frontino, Filippo De Luca, Fortunato Lombardo, Giusy Salzano, Lorenzo Iughetti, Adriana Franzese, Pietro Buono, Ilaria De Simone, Francesco Prisco, Alessandra Cocca, Franco Cadario, Carla M. Monciotti, Valentina Savio, Francesca Cardella, Maurizio Vanelli, Giovanni Chiari, Katrin Errico, Brunella Iovane, Valeria Calcaterra, Francesco Citro, Sandro Cantoni, Alberto Marsciani, Marco Cappa, Patrizia I. Patera, Riccardo Schiaffini, Nicoletta Sulli, Marialuisa Spoletini, Franco Cerutti, Ivana Rabbone, Sabrina Sicignano, Vittoria Cauvin, Maria Bellizzi, Giorgio Tonini, Elena Faleschini, Alessandro Salvatoni, Leonardo Pinelli, Claudio Maffeis, Giovanna Contreas

Research output: Contribution to journalArticle

Abstract

Context: The incidence of type 1 diabetes has been increasing over time. Objective: We estimated the genetic and environmental components of type 1 diabetes susceptibility in a twin cohort of recent-onset cases to explore the sources of changing disease epidemiology. Design: We linked the population-based Italian Twin Registry with 14803 type 1 diabetes records from 36 pediatric diabetes care centers throughout Italy, except Sardinia, and identified 173 diabetic twins. Patients were positive for at least one autoantibody to islet cell, glutamate decarboxylase, tyrosine phosphatase, insulin, or zinc transporter 8 and were insulin dependent since their diagnosis. Zygosity was determined by DNA genotyping or by questionnaire. Outcome Measures: We estimated proband-wise concordance, cotwin recurrence risk with Kaplan-Meier method, and genetic and environmental proportions of susceptibility variance by structural equation models. Results: We recruited 104 diabetic twins (53 males) from 88 pairs (34 monozygotic, 54 dizygotic) and one triplet. The mean age at diagnosis was 8.1 yr (range 1.1-20.5 yr), and the median year of diagnosis was 2002. Proband-wise concordances were 45.5 and 16.4% in monozygotic and dizygotic pairs (P = 0.01). Recurrence risks in monozygotic and dizygotic cotwins were 37 and 12% after 10 yr from the proband's diagnosis (P = 0.005). Genetic contribution to type 1 diabetes susceptibility was 40% (95% confidence interval 8-78), and the shared and individual-specific environmental components were 51% (14-77) and 9% (4 -19), respectively. Conclusions: In addition to the moderate genetic effects on type 1 diabetes susceptibility, our results draw attention to the substantial shared environmental effects, suggesting that exposures in fetal or early postnatal life may contribute to the increasing incidence of the disease.

Original languageEnglish
JournalJournal of Clinical Endocrinology and Metabolism
Volume97
Issue number8
DOIs
Publication statusPublished - Aug 2012

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism

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