Hoffjan S, Epplen JTThe genetics of atopic dermatitis: recent findings and future options. J Mol Med (Berl) 83:682-692
ABSTRACT 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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- "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). "
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 · 1.75 Impact Factor
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- "Canine AD is therefore a good model and homologue for the counterpart human condition. It has been clearly demonstrated that human AD is a complex disease with several genetic factors contributing to the pathology observed (Cookson 2004; Hoffjan and Epplen 2005). Genes involved in skin barrier formation, and the adaptive and innate immune systems have all been implicated in the aetiopathogenesis of human AD. "
ABSTRACT: In humans, genome-wide association studies (GWAS) have been shown to be an effective and thorough approach for identifying polymorphisms associated with disease phenotypes. Here, we describe the first study to perform a genome-wide association study in canine atopic dermatitis (cAD) using the Illumina Canine SNP20 array, containing 22,362 single-nucleotide polymorphisms (SNPs). The aim of the study was to identify SNPs associated with cAD using affected and unaffected Golden Retrievers. Further validation studies were performed for potentially associated SNPs using Sequenom genotyping of larger numbers of cases and controls across eight breeds (Boxer, German Shepherd Dog, Labrador, Golden Retriever, Shiba Inu, Shih Tzu, Pit Bull, and West Highland White Terriers). Using meta-analysis, two SNPs were associated with cAD in all breeds tested. RS22114085 was identified as a susceptibility locus (p?=?0.00014, odds ratio?=?2) and RS23472497 as a protective locus (p?=?0.0015, odds ratio?=?0.6). Both of these SNPs were located in intergenic regions, and their effects have been demonstrated to be independent of each other, highlighting that further fine mapping and resequencing is required of these areas. Further, 12 SNPs were validated by Sequenom genotyping as associated with cAD, but these were not associated with all breeds. This study suggests that GWAS will be a useful approach for identifying genetic risk factors for cAD. Given the clinical heterogeneity within this condition and the likelihood that the relative genetic effect sizes are small, greater sample sizes and further studies will be required.Immunogenetics 12/2009; 61(11):765-772. DOI:10.1007/s00251-009-0402-y · 2.49 Impact Factor
- "Because of this nature, the approach is therefore limited in its potential for the discovery of novel targets and pathways. To date, several candidate genes have been identified in AD (Chien et al., 2007; Hoffjan and Epplen, 2005; Morar et al., 2006), which can be categorized into two groups: (1) genes involved in skin barrier function and (2) genes involved in the immune response. "