Analysis of intronic SNP (rs4147358) and expression of SMAD3 gene in Atopic Dermatitis: A case-control study

Immunobiology. 2023 May;228(3):152390. doi: 10.1016/j.imbio.2023.152390. Epub 2023 Apr 23.

Abstract

Background: Atopic Dermatitis (AD) is a multifactorial cutaneous disorder associated with chronic inflammation of the skin. Growing evidence points to TGF-β/SMAD signaling as a key player in mediating inflammation and the subsequent tissue remodeling, often resulting in fibrosis. This study investigates the role of a core transcription factor involved in TGF-β signaling i.e., SMAD3 genetic variants (rs4147358) in AD predisposition and its association with SMAD3 mRNA expression, serum IgE levels, and sensitization to various allergens in AD patients.

Methods: A total of 246 subjects including 134 AD cases and 112 matched healthy controls were genotyped for SMAD3 intronic SNP by PCR-RFLP. mRNA expression of SMAD3 was determined by quantitative Real-Time PCR (qRT-PCR), Vitamin-D levels by chemiluminescence, and total serum IgE levels by ELISA. In-vivo allergy testing was performed for the evaluation of allergic reactions to house dust mites (HDM) and food allergens.

Results: A significantly higher frequency of mutant genotype AA (cases: 19.4% vs controls: 8.9%) (OR = 2.8, CI = 1.2 - 6.7, p = 0.01) was observed in AD cases. The mutant allele 'A' also showed a 1.9-fold higher risk for AD compared to the wild allele 'C' indicating that the carriers of the A allele have a higher risk for AD predisposition (OR-1.9, CI = 1.3-2.8, p < 0.001). In addition, quantitative analysis of SMAD3 mRNA in peripheral blood showed 2.8-fold increased expression in AD cases as compared to healthy controls. Stratification analysis revealed the association of the mutant AA genotype with deficient serum Vitamin D levels (p = 0.02) and SMAD3 mRNA overexpression with HDM sensitization (p = 0.03). Furthermore, no significant association of genotypes with SMAD3 mRNA expression was observed.

Conclusion: Our study indicates that SMAD3 intronic SNP bears a significant risk of AD development. Moreover, overexpression of SMAD3 mRNA and its association with HDM sensitization highlights the possible role of this gene in AD pathogenesis.

Keywords: Atopic Eczema; Atopic dermatitis; SMAD3 mRNA expression; SMAD3 polymorphism; TGF-β/SMAD signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allergens
  • Animals
  • Case-Control Studies
  • Dermatitis, Atopic*
  • Food Hypersensitivity*
  • Humans
  • Immunoglobulin E
  • Inflammation
  • Pyroglyphidae
  • Smad3 Protein
  • Transforming Growth Factor beta

Substances

  • Immunoglobulin E
  • Allergens
  • Transforming Growth Factor beta
  • SMAD3 protein, human
  • Smad3 Protein