Hoffjan S, Epplen JTThe genetics of atopic dermatitis: recent findings and future options. J Mol Med (Berl) 83:682-692

Department of Human Genetics, Ruhr-University, Universitätsstrasse 150, 44801 Bochum, Germany.
Journal of Molecular Medicine (Impact Factor: 5.11). 10/2005; 83(9):682-92. DOI: 10.1007/s00109-005-0672-2
Source: PubMed


Atopic dermatitis (AD) is a chronic pruritic skin disease affecting up to 15% of children in industrialized countries. AD belongs to the group of allergic disorders that include food allergy, allergic rhinitis, and asthma. A multifactorial background for AD has been suggested, with genetic as well as environmental factors influencing disease development. Genome-wide screens for AD have been completed in four different populations to date. Interestingly, the susceptibility regions identified for AD show little overlap with asthma susceptibility regions, suggesting that, at least in part, separate genes might be involved in the pathogenesis of the different atopic disorders. Instead, some of the identified regions overlap with susceptibility regions for psoriasis, another chronic skin disease. Thus, genes expressed in the skin might play an important role in AD pathogenesis, in addition to genes influencing atopic diatheses. Although no veritable "AD gene" has been identified by positional cloning to date, examples from other complex genetic disorders such as asthma show that this goal is likely to be reached in the near future. Candidate gene studies, on the other hand, have identified 19 genes that were shown to be associated with AD in at least one study. The results of genome-wide screens as well as candidate gene studies are evaluated here in detail.

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    • "Tacrolimus and Pimecrolimus are topical calcineurin inhibitors (TCI). These steroidal-free alternatives in the treatment of the inflammatory response in AD constitute the second line therapy in AD [61]. The action mechanism of TCI is limited to immune cells only, thus skin atrophy or telangiectasia are not observed, contrary to TCS [62]. "
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    ABSTRACT: Atopic dermatitis is a multifactorial, chronic relapsing, inflammatory disease, characterized by xerosis, eczematous lesions, and pruritus. The latter usually leads to an "itch-scratch" cycle that may compromise the epidermal barrier. Skin barrier abnormalities in atopic dermatitis may result from mutations in the gene encoding for filaggrin, which plays an important role in the formation of cornified cytosol. Barrier abnormalities render the skin more permeable to irritants, allergens, and microorganisms. Treatment of atopic dermatitis must be directed to control the itching, suppress the inflammation, and restore the skin barrier. Emollients, both creams and ointments, improve the barrier function of stratum corneum by providing it with water and lipids. Studies on atopic dermatitis and barrier repair treatment show that adequate lipid replacement therapy reduces the inflammation and restores epidermal function. Efforts directed to develop immunomodulators that interfere with cytokine-induced skin barrier dysfunction, provide a promising strategy for treatment of atopic dermatitis. Moreover, an impressive proliferation of more than 80 clinical studies focusing on topical treatments in atopic dermatitis led to growing expectations for better therapies.
    Dermatology Research and Practice 08/2012; 2012:923134. DOI:10.1155/2012/923134
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    • "AA blood gene expression profiles differentiate AA patients with a history of atopy and reveal altered gene expression at suggested atopy susceptibility loci While a significant proportion of AA patients (up to 60%) have concomitant atopic disease, the genetic risk factors for this association are unknown. Of note, 5 of the 6 transcriptional " hot spots " found within the AA blood and skin gene expression signatures coincide with regions previously reported to be relevant to atopic dermatitis (AD) susceptibility [22] [23] (Fig. 1). These data support evidence of a shared genetic background in patients with AA and AD. "
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    ABSTRACT: Alopecia areata (AA), a non-scarring inflammatory hair loss disorder, is a complex disease determined by genetic and environmental factors that remain largely unknown. Re-analysis of genome-wide microarray data in 9 patient blood and 10 skin samples revealed transcriptional "hot spots" at chromosomes 1q21-q32, 11q12-q14, and 16p13-p13.3 (blood) and 6p21.3, 12q12-q13, and 17q12-q24 (skin) harboring high densities of dysregulated genes. We then integrated AA associated gene expression profiles with previous genome-wide genetic analyses to identify a subset of 112 dysregulated genes that map to putative susceptibility loci. Finally, we analyzed AA patients stratified by defined clinical characteristics, including a history of atopy, autoimmune disease, and nail disease, thus deconstructing the clinical heterogeneity observed among AA patients. Integrated chromosomal and transcriptional profiling identified several dysregulated chromosomal regions and genes representing an enriched set of biomarkers relevant to AA pathogenesis and clinical heterogeneity.
    Genomics 09/2011; 98(6):431-9. DOI:10.1016/j.ygeno.2011.08.009 · 2.28 Impact Factor
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    • "In humans, it has been established that AD is a complex disease with several genetic factors (Hoffjan and Epplen, 2005). Genetic research into cAD is limited, although the strong breed association provides evidence of genetic links (Sousa and Marsella, 2001; Tarpataki et al., 2006). "
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    ABSTRACT: Canine atopic dermatitis (cAD) is a common, severe pruritic and inflammatory skin disease and is a major veterinary welfare issue. This study genotyped 97 single nucleotide polymorphisms (SNPs) in 25 candidate genes in 659 dogs across eight breeds from three locations (UK, USA and Japan). These genes were selected from hAD literature, and previous cAD gene expression experiments. The aim of this study was to identify any shared gene associations between cAD and hAD. Only one SNP within the TSLP-receptor was associated with all eight breeds (corrected p=0.037). Five SNPs within Filaggrin, DPP4, MS4A2, and INPPL1 were associated with cAD, but only in certain breeds from different locations. Though these associations are broadly similar to hAD the variability of results across the breeds and locations demonstrates that a candidate gene approach using mixed breeds from different locations is not appropriate. This study therefore suggests that further candidate gene studies in cAD should be breed and location specific to increase the likelihood of finding associations with the disease.
    Veterinary Immunology and Immunopathology 12/2010; 138(3):193-7. DOI:10.1016/j.vetimm.2010.07.020 · 1.54 Impact Factor
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