Atopic Eczema: Genetic Associations and Potential Links to Developmental Exposures

Abstract

Atopic eczema (AE), or atopic dermatitis (AD), is a common inflammatory skin disease with a disrupted epidermal barrier and an allergic immune response. AD/AE is prominently characterized by a symptomatic itch and transient skin lesions. Infants compose a significant percentage affected. Two models have been proposed to explain AD/AE skin pathology: the gut microbiome-focused inside-outside model and the outside-inside model concentrating on the disrupted skin barrier/skin microbiome. Gene disruptions contributing to epidermal structure, as well as those in immune system genes, are implicated. Over 30 genes have been linked to AD/AE with Flg and Tmem79/Matt alterations being common. Other linked disruptions are in the interleukin-1 family of cytokines/receptors and the T2 gene family of cytokines. Inheritable epigenetic modifications of the genes or associated proteins may also be involved. Skin barrier disruption and the allergic immune response have been the main foci in mechanistic studies of AD/AE, but the role of the environment is becoming more apparent. Thus, an examination of in utero exposures could be very helpful in understanding the heterogeneity of AD/AE. Although research is limited, there is evidence that developmental exposure to environmental tobacco smoke or phthalates may impact disease. Management for AD/AE includes topical corticosteroids and calcineurin inhibitors, which safely facilitate improvements in select individuals. Disease heterogeneity warrants continued research not only into elucidating disease mechanism(s), via identification of contributing genetic alterations, but also research to understand how/when these genetic alterations occur. This may lead to the cure that those affected by AD/AE eagerly await.

Genetics and Epigenetics of Atopic Dermatitis: An Updated Systematic Review

“…In this sense, miR-151a and hsa-mir-144-3p have been proposed as potential biomarkers in AD, as they have been shown to be differentially expressed in serum and umbilical cord serum, respectively [26,30]. miR-151a would reduce IL12RB2 levels in T-cells, favouring the increase of Th2 cells, which are central in the pathogenesis of AD [30,183]. Also, an increased expression of miR-144 would reduce ABCA1 mRNA and protein levels and induce a proinflammatory response via NF-κβ [26].…”

Dietary Protein Intake and Associated Risks for Atopic Dermatitis, Intrinsic Eczema, and Allergic Sensitization among Young Chinese Adults in Singapore/Malaysia: Key Findings from a Cross-sectional Study

“…Despite most patients with AD suffering from similar clinical symptoms, including intense itching and recurrent inflamed rash, the severity of symptoms and underlying causes of the disease vary from person to person ( Chovatiya and Silverberg, 2022 ). The disease pathogenesis of AD is complex and multifactorial, in which numerous synergized factors, including genetic, biological, environmental, lifestyles, and even dietary habits, interact to complicate AD development ( Bauer, 2017 ; Brown et al., 2020 ; Ng and Chew, 2020 ). Recent findings have suggested a strong association between specific dietary patterns or nutrients and AD ( Khan et al., 2022 ; Lim et al., 2022 ; Silverberg et al., 2016 ).…”

Dysbiotic Lesional Microbiome With Filaggrin Missense Variants Associate With Atopic Dermatitis in India

“…AD affects about 20% of children and 10% of adults worldwide (Clausen et al, 2018). Variants in genes involved in maintenance of skin integrity (FLG, ACTL9, SPINK5) and inflammation (TNFA, IL10, IL13) have previously been found associated with AD (Kato et al, 2003;Bussmann et al, 2011;Lesiak et al, 2011;Paternoster et al, 2011;Behniafard et al, 2012;Portelli et al, 2015;Bauer, 2017;Kim and Leung, 2018). Loss-offunction (LoF) mutations in Filaggrin (FLG) gene, that encodes a protein responsible for maintaining skin barrier function, have been consistently found to be associated with AD.…”