The Genetics and Epigenetics of Atopic Dermatitis-Filaggrin and Other Polymorphisms

Clin Rev Allergy Immunol. 2016 Dec;51(3):315-328. doi: 10.1007/s12016-015-8508-5.


Atopic dermatitis (AD) is a chronic inflammatory skin disease caused by a combination of genetic and environmental factors. Genetic evidences depict a complex network comprising by epidermal barrier dysfunctions and dysregulation of innate and adaptive immunity in the pathogenesis of AD. Mutations in the human filaggrin gene (FLG) are the most significant and well-replicated genetic mutation associated with AD, and other mutations associated with epidermal barriers such as SPINK5, FLG-2, SPRR3, and CLDN1 have all been linked to AD. Gene variants may also contribute to the abnormal innate and adaptive responses found in AD, including mutations in PRRs and AMPs, TSLP and TSLPR, IL-1 family cytokines and receptors genes, vitamin D pathway genes, FCER1A, and Th2 and other cytokines genes. GWAS and Immunochip analysis have identified a total of 19 susceptibility loci for AD. Candidate genes at these susceptibility loci identified by GWAS and Immunochip analysis also suggest roles for epidermal barrier functions, innate and adaptive immunity, interleukin-1 family signaling, regulatory T cells, the vitamin D pathway, and the nerve growth factor pathway in the pathogenesis of AD. Increasing evidences show the modern lifestyle (i.e., the hygiene hypothesis, Western diet) and other environmental factors such as pollution and environmental tobacco smoke (ETS) lead to the increasing prevalence of AD with the development of industrialization. Epigenetic alterations in response to these environmental factors, including DNA methylation and microRNA related to immune system and skin barriers, have been found to contribute to the pathogenesis of AD. Genetic variants and epigenetic alteration might be the key tools for the molecular taxonomy of AD and provide the background for the personalized management.

Keywords: Atopic dermatitis; Epidermal barrier; Epigenetics; Filaggrin; Genetics; Polymorphism.

Publication types

  • Review

MeSH terms

  • Animals
  • Cytokines / genetics
  • Dermatitis, Atopic / genetics*
  • Dermatitis, Atopic / immunology
  • Dermatitis, Atopic / metabolism
  • Environment
  • Epidermis / metabolism
  • Epidermis / pathology
  • Epigenesis, Genetic*
  • Filaggrin Proteins
  • Gene-Environment Interaction
  • Genetic Association Studies*
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study
  • Humans
  • Immune System / cytology
  • Immune System / immunology
  • Immune System / metabolism
  • Intermediate Filament Proteins / genetics*
  • Intermediate Filament Proteins / metabolism
  • Mutation
  • Polymorphism, Genetic*
  • Receptors, Cytokine / genetics


  • Cytokines
  • FLG protein, human
  • FLG2 protein, human
  • Filaggrin Proteins
  • Intermediate Filament Proteins
  • Receptors, Cytokine