Atopic Dermatitis (AD), also known as Atopic eczema (AE), is a heterogeneous inflammatory disorder of the skin with varying phenotypes and clinical presentations (Bieber et al., 2017), affecting people of almost all ages, with most of the cases (∼80 %) typically starting in infancy or childhood (Silverberg et al., 2021). The condition is characterized by sensitive, dry, and severe pruritic skin with recurrent eczematous lesions leading to poor quality of life and substantial psychosocial impact on patients as well as relatives (Zeiser et al., 2021). AD is not merely a skin disorder but is related to a vast array of other atopic conditions, including food allergy, allergic rhinitis, allergic asthma, as well as greater risk of psychological repercussions. (Silverberg, 2019) Globally, AD accounts for one of the greatest burden of skin diseases (Hay et al., 2014) with increasing prevalence rate afflicting as many as 20 % of children and 10 % of adults in high socioeconomic nations (Silverberg and Hanifin, 2013, Odhiambo et al., 2009).

The pathophysiology of AD is multifactorial and involves genetic susceptibility, epidermal barrier dysfunction, environmental agents, and immune dysregulation (Nomura and Kabashima, 2016, Egawa and Kabashima, 2016). The imbalance between Th-1 / Th-2 cytokines is fundamental to the pathophysiology of AD. Additionally, genes encoding multiple other functional cytokines have also been implicated using candidate gene studies. The transforming growth factor-β (TGF- β) is a class of pleiotropic cytokines comprising three isoforms: TGF- β1, TGF- β2, and TGF- β3, among which TGF- β1 is the chief form involved in immune system homeostasis and has diverse outcomes on a wide range of immune and non-immune cell types.

TGF-β1 is encoded by a gene located on chromosome 19q13.2 region, comprising seven exons (Martelossi Cebinelli et al., 2016), and is involved in numerous biological processes such as immune response regulation, differentiation, proliferation, and activation of immune cells, wound healing, angiogenesis, hematopoiesis, etc., besides being incriminated of immune abnormalities attributed to autoimmunity, cancer, and fibrosis (Prud’homme and Piccirillo, 2000). There is mounting evidence supporting the role of TGF- β1 in mediating inflammation in allergic diseases (TGFβ Receptor Mutations Impose a Strong Predisposition for Human Allergic Disease. Accessed May 11, 2022. https://www.science.org/doi/abs/10.1126/scitranslmed.3006448, Weissler and Frischmeyer-Guerrerio, 2019) as well as in subsequent tissue remodeling (Yang et al., 2012). Moreover, it acts as a fibrogenic and immunomodulatory factor and can induce differentiation of fibroblasts and extracellular matrix deposition of collagen and fibronectin (Frangogiannis, 2020), thus playing a pivotal role in the remodeling of the affected tissue following multiple episodes of damage and repair in chronic stages of Allergic Asthma, (Redington et al., 1997, Vignola et al., 1997) and AD (Toda et al., 2003).

Genetic variations within TGF-β1 gene including eight SNPs (rs11466313, rs11466314, rs11466316, rs1800468, rs1800469, rs1800470, rs1800471, and rs2317130) in addition to one deletion/insertion (I/D) polymorphism have been reported to alter TGF-β1 expression (TGF-β1 functional polymorphisms: a review | SpringerLink. Accessed May 11, 2022. https://link.springer.com/article/10.1684/ecn.2016.0382) either by regulation of transcription or its protein synthesis (Martelossi Cebinelli et al., 2016, Grainger et al., 1999, Awad et al., 1998). Some of these have been established in AD and have been described to affect TGF- β1 production in these patients (Arkwright et al., 2001, Behniafard et al., 2018). The prominent ones include polymorphism at codon 10 (Leu10Pro/rs1800470) which replaces the amino acid from leucine to proline and is linked to higher TGF-β1 synthesis and at codon 25 (Arg25Pro/rs1800471, from arginine to proline, which is linked to lower TGF-β1 synthesis. As of yet, the role of SNPs -509C/T (rs1800469) and -800 G/A (rs1800468) located in the promoter area of TGF-β1 have not been evaluated in AD. Therefore, the current study seeks to ascertain the function of these promoter polymorphisms in AD susceptibility, as well as their association with TGF- β1 mRNA and serum levels in the peripheral blood of these patients and adjusted healthy controls. The study will be first of its kind to evaluate the concomitant role of functional SNPs of TGF-β1 in the promoter area and its expression levels in AD which could contribute to a better understanding of the role of this gene in the pathophysiology of AD and development of comprehensive strategies to treat the disease.