Twin Studies of Atopic Dermatitis: Interpretations and Applications in the Filaggrin Era

Camilla Elmose,Simon Francis Thomsen

doi:10.1155/2015/902359

Camilla Elmose, Simon Francis Thomsen

Open Access

https://doi.org/10.1155/2015/902359

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Journal: Journal of Allergy	Publication Date: Sep 10, 2015
Citations: 41	License type: CC BY 3.0

Affiliation: Bispebjerg Hospital, University of Copenhagen

Abstract

Aim. The aim of this study was to conduct a systematic review of population-based twin studies of (a) the concordance and heritability of AD and (b) the relationship between AD and asthma and, furthermore, to reinterpret findings from previous twin studies in the light of the emerging knowledge about filaggrin and its role in the atopic march and provide suggestions for future research in this area. Methods. We identified all twin studies (published after 1970) that have calculated the concordance rate and/or the heritability of AD, or the genetic and environmental correlations between AD and asthma. Results. Reported concordance rates for AD ranged, respectively. From 0.15 to 0.86 for MZ and from 0.05 to 0.41 for DZ twins, with an overall ratio of MZ : DZ twins of approximately three. The heritability of AD was estimated to be approximately 75%, and the association between AD and asthma was around 85% explained by genetic pleiotropy. Conclusions. Genetic factors account for most of the variability in AD susceptibility and for the association between AD and asthma. Controversy remains as to whether the atopic diseases are causally related or whether they are diverse clinical manifestations of a common, underlying (genetic) disease trait. Future twin studies may help solve this enigma.

Highlights

Atopic dermatitis (AD) is a common, inflammatory skin disease that primarily affects small children. 50% of cases appear within the first year of life, while 95% of cases have an onset before the age of five [1]
The second hypothesis is the so-called leaky skin barrier hypothesis, which is based on the observation that individuals with mutations in the filaggrin gene (FLG), which encodes the epidermal structural protein filaggrin, are at increased risk of developing AD [6]
The reviewed studies vary in terms of age group, period, and country of origin, they all show that MZ twins are more concordant for AD than are DZ twins with a ratio between these concordances of around three, demonstrating great importance of genetic factors in the development of AD

Summary

Introduction

Atopic dermatitis (AD) is a common, inflammatory skin disease that primarily affects small children. 50% of cases appear within the first year of life, while 95% of cases have an onset before the age of five [1]. It is generally accepted that the rise in prevalence of AD, at least in part, can be explained by widespread environmental hygienic changes occurring in the last part of the 20th century. These changes are thought to have led to pronounced changes in the human microflora impacting pre- and perinatally on the risk of AD and other atopic diseases via complex interactions with the host immune system [4]. Individuals with FLG mutations experience a disrupted skin barrier, phenotypically characterized by dry, fissured skin, facilitating penetration of allergens, immunological dysfunction, and an increased risk of developing eczema. Up to 50% of all patients with AD carry FLG mutations, making it the strongest known risk factor for AD [6]

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Conclusion