How is "Dermal Sensitivity" encoded by the genome?
Why is skin so important? The skin is the largest organ, and it covers and protects the entire body from stimulants such as bacteria, dirt, and other foreign objects. Skin sensitivity, also known as dermal sensitivity, is caused by an immunologic response to various environmental triggers and allergens. Many children with atopic dermatitis (AD) have asthma and AD shares regions of genetic linkage with psoriasis, another chronic inflammatory skin disease. Hallmarks of atopic dermatitis include dry, itchy skin and red rashes that come and go. Genetics, environmental triggers and skin barrier dysfunction may be involved in susceptibility to dermal sensitivity.
Two genome-wide association studies (GWASs) identified the genetic factor of dermal sensitivity in a large number of samples. In the first study, researchers performed a GWAS of childhood-onset atopic dermatitis (AD). The discovery phase comprised 1563 childhood with moderate to severe AD cases of European descent and 4054 population controls of matched ancestry. Overall, 36.4% of the cases also had a doctor's diagnosis of asthma. A total of 47 single nucleotide polymorphisms (SNPs) associated with AD found in the discovery phase were later assessed for replication in the second panel of 2286 European cases and 3160 European controls. Associations were with the same allele and in the same direction as the discovery phase. When participants with AD but not asthma were compared with controls, rs1469621 in the THSD7B gene, rs8111 in the ATF6B gene, rs4750646, and rs4782695 in the GSE1 gene were related to AD with marginal significance.
While this study is well powered for detecting common effects underpinning the genetic origins of AD, it has some limitations. Asthma status was not available in our population-based cohorts, increasing the potential for misclassification bias. This may have resulted in a loss of statistical power, given the prevalence of phenotypes studied. If you would like to know more about this research, you can read the study here:
https://www.ncbi.nlm.nih.gov/pubmed/23886662
In the second study, researchers performed a GWAS of atopic dermatitis (AD) in a Chinese Han population using 1,012 affected individuals (cases) and 1,362 controls, followed by a replication study in an additional 3,624 cases and 12,197 controls of Chinese Han ethnicity (replication1 and 2), as well as 1,806 cases and 3,256 controls from Germany (replication3). The 19 most promising single nucleotide polymorphisms (SNPs) were analyzed in the initial validation study in 276 controls for the replication 1 sample and 3,956 controls for the replication 2 sample. The association analysis showed supportive evidence for rs11204971, rs7701890 in the TMEM232 gene, rs17173197 in the PRKAG2 gene, rs2393903, rs6010620 near the RTEL1gene with AD. In addition, the rs6010620 also showed a relationship with AD with marginal significance in the German population. Rs6010620 is also located close to the TNFRSF6B gene and the ZGPAT gene, and the SNP might be associated with TNFRSF6B and ZGPAT expression. TNFRSF6B has an important role in adaptive immune responses, while ZGPAT encodes a zinc finger CCCH domain–containing protein that is involved in the epidermal growth factor receptor (EGFR) pathway. EGFR is over-expressed in lesional skin of individuals with atopic dermatitis, and blocking EGFR induces dysregulated chemokine expression in keratinocytes and leads to enhanced skin inflammation.
These results indicate that TNFRSF6B and ZGPAT are plausible candidate genes for atopic dermatitis.
However, further studies in additional and ethnically diverse cohorts are needed to increase our understanding of atopic dermatitis's complex genetic architecture and gain better insights into its proposed genetic heterogeneity. If you would like to know more about this research, you can read the study here:
https://www.ncbi.nlm.nih.gov/pubmed/21666691
Are you interested in learning more about your genetic tendency for dermal sensitivity? You can log in to your Genomelink TRAITS to see this new genetic trait.
