Major limitations of published studies were low numbers of individuals with AD and FLG loss-of-function mutations and exposure to specific environmental factors (n=5 to 94), and variation in exposure definitions.
Fifteen percent of atopic dermatitis (AD) liability-scale heritability could be attributed to 31 susceptibility loci identified by using genome-wide association studies, with only 3 of them (IL13, IL-6 receptor [IL6R], and filaggrin [FLG]) resolved to protein-coding variants.
The presence of loss-of-function mutations in the filaggrin gene (FLG) is the main predisposing factor for AD FLG mutations show ethnic and geographical variations, even between European populations.
Abundant corneocyte surface protrusions, observed in patients with atopic dermatitis with filaggrin loss-of-function mutations, are inversely associated with levels of natural moisturizing factors (NMFs) in the stratum corneum.
Filaggrin (FLG) loss of function variants have been associated with the onset and severity of atopic dermatitis and are the most common genetic association with AD.
Multiple factors are associated with colonization of AD skin by <i>S. aureus</i>, including the strength of <i>S. aureus</i>-corneocyte adhesion, deficiency of antimicrobial peptides, decreased levels of filaggrin and filaggrin degradation products, overexpressed Th2/Th17 cytokines, microbial dysbiosis and altered lipid profiles.<i>S. aureus</i> colonization on AD skin causes skin barrier dysfunction through virulence factors such as superantigens (toxins), enzymes and other proteins.
These results suggest that β-carotene reduces skin inflammation through the suppressed expression of inflammatory factors or the activity of MMPs as well as the promotion of filaggrin expression in AD-like skin.
A randomized controlled trial of an emollient with ceramide and filaggrin-associated amino acids for the primary prevention of atopic dermatitis in high-risk infants.
FLG loss-of-function mutations were significantly associated with AD onset in infancy (≤2 years) (P < 0.001, OR 3.54, 95% CI 1.88-6.65), but not with AD onset in childhood (≥3 years) (P = 0.981, OR 0.99, 95% CI 0.29-3.36), and none of the children in the present cohort who developed AD at 5 years of age or later carried FLG loss-of-function mutations.
In this review we summarised (emphasized) recent findings in understanding the role of filaggrin in atopic dermatitis and other diseases, participants in the atopic march.
The discovery of the filaggrin gene was important in the emerging model for AD pathogenesis, combining skin barrier function with adaptive and innate immunity.
Then, we assessed the proliferation and the production of the Th22 chemokines CCR4 and CCR10 by ICOSL-stimulated AD peripheral blood mononuclear cells (PBMCs) as well as their effects on keratinocyte filaggrin production.
Children with early, late transient and persistent eczema more often had a filaggrin mutation or additional risk alleles (range OR: 1.07, 95%CI 1.02-1.12 and OR 2.21, 95%CI 1.39-3.50).
We then tested the impact of the choice of the most common definitions of 'cases' and 'controls' on AD prevalence estimates and associated risk factors (including filaggrin mutations) among children aged 5 years in two population-based birth cohorts: the Manchester Asthma and Allergy Study (MAAS) and Asthma in Ashford.
Filaggrin and the proportion of ω-hydroxy fatty acid sphingosine ceramide content in nonlesional skin of children with AD <i>FA</i>+ were substantially lower than in AD <i>FA</i>- and NA skin.