Emerging Effects of Early Environmental Factors over Genetic Background for Type 1 Diabetes Susceptibility: Evidence from a Nationwide Italian Twin Study (original) (raw)

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1Genetic Epidemiology Unit (L.N., C.F., R.C., V.T., M.A.S.), National Institute of Health, National Centre of Epidemiology, Surveillance, and Health Promotion, 00161 Rome, Italy

*Address all correspondence and requests for reprints to: Lorenza Nisticò, M.D., Ph.D., Istituto Superiore di Sanità, Centro Nazionale di Epidemiologia, Sorveglianza e Promozione della Salute, Reparto di Epidemiologia Genetica, Viale Regina Elena, 299, 00161 Roma, Italia.

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2Department of Pediatrics (D.I., A.G.), Regional Centre of Pediatric Diabetology “G. Stoppoloni,” Second University of Naples, 80138 Naples, Italy

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2Department of Pediatrics (D.I., A.G.), Regional Centre of Pediatric Diabetology “G. Stoppoloni,” Second University of Naples, 80138 Naples, Italy

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1Genetic Epidemiology Unit (L.N., C.F., R.C., V.T., M.A.S.), National Institute of Health, National Centre of Epidemiology, Surveillance, and Health Promotion, 00161 Rome, Italy

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1Genetic Epidemiology Unit (L.N., C.F., R.C., V.T., M.A.S.), National Institute of Health, National Centre of Epidemiology, Surveillance, and Health Promotion, 00161 Rome, Italy

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1Genetic Epidemiology Unit (L.N., C.F., R.C., V.T., M.A.S.), National Institute of Health, National Centre of Epidemiology, Surveillance, and Health Promotion, 00161 Rome, Italy

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1Genetic Epidemiology Unit (L.N., C.F., R.C., V.T., M.A.S.), National Institute of Health, National Centre of Epidemiology, Surveillance, and Health Promotion, 00161 Rome, Italy

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the Study Group on Diabetes of the Italian Society of Pediatric Endocrinology and Diabetology

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Received:

23 December 2011

Published:

01 August 2012

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Lorenza Nisticò, Dario Iafusco, Alfonso Galderisi, Corrado Fagnani, Rodolfo Cotichini, Virgilia Toccaceli, Maria Antonietta Stazi, the Study Group on Diabetes of the Italian Society of Pediatric Endocrinology and Diabetology, Emerging Effects of Early Environmental Factors over Genetic Background for Type 1 Diabetes Susceptibility: Evidence from a Nationwide Italian Twin Study, The Journal of Clinical Endocrinology & Metabolism, Volume 97, Issue 8, 1 August 2012, Pages E1483–E1491, https://doi.org/10.1210/jc.2011-3457
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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.

Copyright © 2012 by The Endocrine Society

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