An update on the genetics of atopic dermatitis: Scratching the surface in 2009

A genetic basis for atopic dermatitis (AD) has long been recognized. Historic documents allude to family history of disease as a risk factor. Before characterization of the human genome, heritability studies combined with family-based linkage studies supported the definition of AD as a complex trait in that interactions between genes and environmental factors and the interplay between multiple genes contribute to disease manifestation. A summary of more than 100 published reports on genetic association studies through mid-2009 implicates 81 genes, in 46 of which at least 1 positive association with AD has been demonstrated. Of these, the gene encoding filaggrin (FLG) has been most consistently replicated. Most candidate gene studies to date have focused on adaptive and innate immune response genes, but there is increasing interest in skin barrier dysfunction genes. This review examines the methods that have been used to identify susceptibility genes for AD and how the underlying pathology of this disease has been used to select candidate genes. Current challenges and the potential effect of new technologies are discussed.

Key words: Atopic dermatitis, genetics, IgE-mediated response, innate immunity, skin barrier dysfunction, genetic association, gene-environment interaction, ethnicity

Abbreviations used: AD, Atopic dermatitis, cM, Centimorgans, EDC, Epidermal differentiation complex, FLG, Filaggrin gene, GWAS, Genome-wide association study, NOD, Nucleotide-binding oligomerization domain, OR, Odds ratio, SC, Stratum corneum, SNP, Single nucleotide polymorphism, TJ, Tight junction, TLR, Toll-like receptor