2010 Update on genetics of atopic dermatitis: Scratching the surface

A genetic basis for atopic dermatitis (AD) has long been recognized. Historic documents point to family history as a risk factor.

AD results from a complex interaction between multiple genes and environmental factors.


Human chromosomes (grey) capped by telomeres (white). Image source: Wikipedia, public domain.

More than 81 genes have been implicated in AD. The gene encoding filaggrin (FLG) has been most consistently replicated. Filaggrin mutations increase the risk for persistent dry skin and eczema independent of sensitization (JACI, 2012).

Most candidate genes have focused on immune response, but there is increasing interest in skin barrier genes.

SNPs associated with atopic diseases

Filaggrin gene

Filaggrin is essential for epidermal barrier function. SNP associated with eczema and asthma.

17q12-21 gene

ORMDL3 protein defects associated with asthma.

5q22-32 gene

CD14 is a lipopolysaccharide (LPS) receptor. SNPs associated with asthma and atopy.

3p21-22 gene

CCR5 is a chemokine receptor. SNP can be protective against asthma.

Xp22 gene

TLR7 and TLR8 are recognition receptors for viral ssRNA. SNPs assciated with asthma, rhinitis, atopic dermatitis.

5q31 gene

IL-13 is a cytokine that induces IgE secretion, mucus production, and collagen synthesis (fibrosis). SNPs associated with asthma.

ADRB2 gene

ADRB2 gene encodes β2-adrenergic receptor. Argenteum (Arg) or Arg/Arg phenotype associated with decreased albuterol response compared to Gly/Gly phenotype at residue 16.

ADAM33 gene

Type 1 transmembrane protein involved in cell-to-cell interactions. SNPs associated with asthma.

References:
An update on the genetics of atopic dermatitis: Scratching the surface in 2009. Kathleen C. Barnes. Journal of Allergy and Clinical Immunology, Volume 125, Issue 1, January 2010, Pages 16-29.e11.

Loss-of-function mutations in filaggrin gene are associated with atopic dermatitis, and now with peanut allergy too. JACI, 2011.

Gene defect can triple risk of peanut allergy - filaggrin has already been shown to be a factor in eczema and asthma. BBC, 2011.
Consumer genomics company 23andMe now tests for hay fever, and atopic dermatitis. Clinical relevance is unclear.