Concordance, disease progression, and heritability of coeliac disease in Italian twins

Lorenza Nisticò ^1*, Corrado Fagnani ¹, Iolanda Coto ², Selvaggia Percopo ², Rodolfo Cotichini ¹, Maria Giovanna Limongelli ², Franco Paparo ², Sandra D'Alfonso ³, Mara Giordano ³, Concettina Sferlazzas ⁴, Giuseppe Magazzù ⁴, Patricia Momigliano-Richiardi ³, Luigi Greco ² and Maria Antonietta Stazi ¹

¹ Genetic Epidemiology Unit, CNESPS, Istituto Superiore di Sanità, Italy
² Department of Paediatrics, University of Naples Federico II, Italy
³ Department of Medical Sciences, Eastern Piedmont University, Italy
⁴ Department of Paediatric Sciences, University of Messina, Italy

^* To whom correspondence should be addressed. E-mail: lorenza.nistico{at}iss.it.

Accepted 28 November 2005

Abstract

Background and aims: We adopted the twin method to disentangle the genetic and environmental components of susceptibility to coeliac disease (CD). We estimated disease concordance rate by zygosity and HLA genotypes, discordance times, progression rates to the disease and heritability.

Methods: We cross-linked the Italian Twin Registry with the membership lists of the Italian Coeliac Disease Association and recruited 23 monozygotic (MZ) and 50 dizygotic (DZ) twin pairs with at least one affected member. Zygosity was assigned by DNA fingerprinting and HLA-DQ and DR alleles were genotyped. Disease status was ascertained by anti-endomysial (EMA), anti-human-tissue- transglutaminase (anti-tTG) antibodies and bowel biopsy.

Results: Concordances were significantly higher in MZ (83.3% probandwise, 71.4% pairwise) than in DZ pairs (16.7% probandwise, 9.1% pairwise). Concordance was not affected by gender or HLA genotype of the co-twin and being MZ was significantly associated with occurrence of CD (Cox adjusted hazard ratio = 14.3; 95% CI: 4.0-50.3). In 90% of concordant pairs the discordance time was 2 years. MZ and DZ co-twins had respectively 70% and 9% cumulative probability to have symptomatic or silent forms of CD within 5 years. Under ACE models with CD population prevalences of 1/91 and 1/1000, the heritability estimates were 87% and 57%, respectively.

Conclusion: MZ pairs have high probability to be concordant regardless of gender or HLA genotype. Most of the affected co-twins receive the diagnosis within 2 years. A remarkable proportion of phenotypic variance is due to genetic factors.

Keywords: coeliac disease, concordance, disease progression, heritability, twin

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