We identified a population-based cohort of Italian twin pairs with at least one diagnosed with type 1 diabetes mellitus (T1DM) to estimate concordance in monozygotic (MZ) and dizygotic (DZ) twins, co-twin recurrence risk and disease discordance time, genetic and environmental components of susceptibility variance to T1DM. Twins were identified linking the Italian Twin Registry with 13,354 T1DM patients records, provided by diabetologists of 35 centers from all over Italy (Sardinia excluded). Out of the 148 pairs/triplets identified, 77 pairs and 1 unlike sex triplet have been enrolled so far. DNA has been collected from saliva of 61 pairs. Zygosity in same sex pairs was assigned by genotyping nine microsatellites or by standardized questionnaire on physical resemblance when DNA was not available: 29 are MZ (17 males) and 48 are DZ (12 and 18 same sex males and females, respectively, and 18 unlike sex). Mean age at diagnosis was 8 yrs (1.1–2.5) in first affected twins and 1.7 yrs (1.4– 19.9) in concordant co-twins. Proband-wise concordances were significantly different (p = .007) between MZ (43.2% [95% CI 23.3– 63.2]) and DZ pairs (11.3% [0–23]). Five years after the diagnosis in the index twins’ cumulative incidences were 35% in MZ co-twins and 6% in DZ co-twins. In concordant pairs, MZ co-twins developed T1DM within 34 days — 5.2 years (median 1.1 yrs) and DZ cotwins within 0 days — 7 yrs (median 4.7 yrs) from diagnoses of the index twins. In discordant pairs, median follow-up times are 4.45 yrs (range: .4–19.0) for MZ and 6.8 yrs (.2–31.8) for DZ unaffected cotwins. Under an ACE model, heritability (A) was estimated at .633 (.159–.893), while contributions of familial (C) and individual-specific (E) environmental effects were .154 (0–.546) and .213 (.107–.366), respectively. This study confirms the substantial contribution of genetics in T1DM susceptibility, with a significant role of individual specific factors. These results are in line with those observed in Finnish and Danish populations. Final results on a larger sample will be shown at the congress.

HERITABILITY OF TYPE 1 DIABETES MELLITUS IN A COHORT OF ITALIAN TWINS

IAFUSCO, Dario;
2010

Abstract

We identified a population-based cohort of Italian twin pairs with at least one diagnosed with type 1 diabetes mellitus (T1DM) to estimate concordance in monozygotic (MZ) and dizygotic (DZ) twins, co-twin recurrence risk and disease discordance time, genetic and environmental components of susceptibility variance to T1DM. Twins were identified linking the Italian Twin Registry with 13,354 T1DM patients records, provided by diabetologists of 35 centers from all over Italy (Sardinia excluded). Out of the 148 pairs/triplets identified, 77 pairs and 1 unlike sex triplet have been enrolled so far. DNA has been collected from saliva of 61 pairs. Zygosity in same sex pairs was assigned by genotyping nine microsatellites or by standardized questionnaire on physical resemblance when DNA was not available: 29 are MZ (17 males) and 48 are DZ (12 and 18 same sex males and females, respectively, and 18 unlike sex). Mean age at diagnosis was 8 yrs (1.1–2.5) in first affected twins and 1.7 yrs (1.4– 19.9) in concordant co-twins. Proband-wise concordances were significantly different (p = .007) between MZ (43.2% [95% CI 23.3– 63.2]) and DZ pairs (11.3% [0–23]). Five years after the diagnosis in the index twins’ cumulative incidences were 35% in MZ co-twins and 6% in DZ co-twins. In concordant pairs, MZ co-twins developed T1DM within 34 days — 5.2 years (median 1.1 yrs) and DZ cotwins within 0 days — 7 yrs (median 4.7 yrs) from diagnoses of the index twins. In discordant pairs, median follow-up times are 4.45 yrs (range: .4–19.0) for MZ and 6.8 yrs (.2–31.8) for DZ unaffected cotwins. Under an ACE model, heritability (A) was estimated at .633 (.159–.893), while contributions of familial (C) and individual-specific (E) environmental effects were .154 (0–.546) and .213 (.107–.366), respectively. This study confirms the substantial contribution of genetics in T1DM susceptibility, with a significant role of individual specific factors. These results are in line with those observed in Finnish and Danish populations. Final results on a larger sample will be shown at the congress.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11591/209728
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