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Unravelling the complex genetic background of atopic dermatitis: from genetic association results towards novel therapeutic strategies

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Abstract

Atopic dermatitis (AD) is a chronic inflammatory skin disease arising from complex interaction between genetic and environmental factors. As the starting point of the so-called “atopic march”, e.g. the progression towards allergic asthma in some but not all affected children, AD has come into focus for potential disease-modifying strategies. To elucidate the genetic factors influencing AD development, linkage, association as well as genome-wide association studies have been performed over the last two decades. The results suggest that besides variation in immune-mediated pathways, an intact skin barrier function plays a key role in AD development. Mutations in the gene encoding filaggrin, a major structural protein in the epidermis, have been consistently associated with AD, especially the early-onset persistent form of disease, and are regarded as the most significant known risk factor for AD development to date. Additionally, variation in some other genes involved in skin integrity and barrier function have shown association with AD. However, the known genetic risk factors can only explain a small part of the heritability at the moment. Whole-exome or whole-genome sequencing studies have not been reported yet, but will probably soon evaluate the influence of rare variations for AD development. Additionally, large multi-centre studies comprehensively incorporating gene–gene and gene–environment interactions as well as epigenetic mechanisms might further elucidate the genetic factors underlying AD pathogenesis and, thus, open the way for a more individualized treatment in the future.

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Abbreviations

AD:

Atopic dermatitis

EDC:

Epidermal differentiation complex

FLG:

Filaggrin

GWAS:

Genome-wide association study

IgE:

Immunoglobulin E

IV:

Ichthyosis vulgaris

MHC:

Major histocompatibility complex

NLR:

NOD-like receptor

PRR:

Pattern recognition receptor

RLR:

RIG-I-like receptor

SNP:

Single nucleotide polymorphism

Th:

T helper lymphocyte

TLR:

Toll-like receptor

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Acknowledgments

We thank Katharina Batzke and Kathrin Bruch for technical assistance.

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The authors declare that they have no competing interests.

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  1. Department of Human Genetics, Ruhr-University Bochum, Universitätsstrasse 150, 44801, Bochum, Germany

    Sabine Hoffjan & Susanne Stemmler

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  1. Sabine Hoffjan
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Correspondence to Sabine Hoffjan.

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Hoffjan, S., Stemmler, S. Unravelling the complex genetic background of atopic dermatitis: from genetic association results towards novel therapeutic strategies. Arch Dermatol Res 307, 659–670 (2015). https://doi.org/10.1007/s00403-015-1550-6

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  • DOI: https://doi.org/10.1007/s00403-015-1550-6

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