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

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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  • Authors+Show Affiliations

    ,

    Department of Human Genetics, Ruhr-University Bochum, Universitätsstrasse 150, 44801, Bochum, Germany. sabine.hoffjan@rub.de.

    Department of Human Genetics, Ruhr-University Bochum, Universitätsstrasse 150, 44801, Bochum, Germany. susanne.stemmler@rub.de.

    Source

    Archives of dermatological research 307:8 2015 Oct pg 659-70

    MeSH

    Adaptive Immunity
    Dermatitis, Atopic
    Gene-Environment Interaction
    Genetic Predisposition to Disease
    Humans
    Immunity, Innate
    Intermediate Filament Proteins
    Skin

    Pub Type(s)

    Journal Article
    Review

    Language

    eng

    PubMed ID

    25693656

    Citation

    Hoffjan, Sabine, and Susanne Stemmler. "Unravelling the Complex Genetic Background of Atopic Dermatitis: From Genetic Association Results Towards Novel Therapeutic Strategies." Archives of Dermatological Research, vol. 307, no. 8, 2015, pp. 659-70.
    Hoffjan S, Stemmler S. Unravelling the complex genetic background of atopic dermatitis: from genetic association results towards novel therapeutic strategies. Arch Dermatol Res. 2015;307(8):659-70.
    Hoffjan, S., & Stemmler, S. (2015). Unravelling the complex genetic background of atopic dermatitis: from genetic association results towards novel therapeutic strategies. Archives of Dermatological Research, 307(8), pp. 659-70. doi:10.1007/s00403-015-1550-6.
    Hoffjan S, Stemmler S. Unravelling the Complex Genetic Background of Atopic Dermatitis: From Genetic Association Results Towards Novel Therapeutic Strategies. Arch Dermatol Res. 2015;307(8):659-70. PubMed PMID: 25693656.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Unravelling the complex genetic background of atopic dermatitis: from genetic association results towards novel therapeutic strategies. AU - Hoffjan,Sabine, AU - Stemmler,Susanne, Y1 - 2015/02/19/ PY - 2014/11/12/received PY - 2015/01/31/accepted PY - 2015/01/14/revised PY - 2015/2/20/entrez PY - 2015/2/20/pubmed PY - 2016/7/1/medline KW - Association KW - Atopic dermatitis KW - Eczema KW - Filaggrin KW - GWAS KW - Personalized therapy SP - 659 EP - 70 JF - Archives of dermatological research JO - Arch. Dermatol. Res. VL - 307 IS - 8 N2 - 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. SN - 1432-069X UR - https://www.unboundmedicine.com/medline/citation/25693656/Unravelling_the_complex_genetic_background_of_atopic_dermatitis:_from_genetic_association_results_towards_novel_therapeutic_strategies_ L2 - https://link.springer.com/article/10.1007/s00403-015-1550-6 DB - PRIME DP - Unbound Medicine ER -