The aim of this study was to examine the association of single nucleotide polymorphisms in the region of the late cornified envelope-like proline-rich 1 (LELP1), hornerin (HRNR) and FLG genes with the course and risk of atopic dermatitis.
The genetic basis is incompletely understood; however, recent studies have shown an association between loss-of-function variants of the filaggrin gene (FLG) and atopic dermatitis.
Recent studies have identified a crucial role for the aryl hydrocarbon receptor (AHR) in controlling the gene expression of filaggrin and other skin barrier proteins, suggesting an underlying association between AHR and AD pathogenesis.
Null mutations in the filaggrin gene (FLG) are strongly associated with moderate to severe AD, but the pathways linking barrier dysfunction and cutaneous inflammation are still largely unknown.
Copenhagen Prospective Study on Asthma in Childhood (COPSAC) was one of the discovery cohorts of the association between eczema and variants in the filaggrin coding gene (FLG).
The objective of this study was to investigate the effects of cumulative exposure to 0.5% sodium lauryl sulphate (SLS) and 0.15% NaOH on the barrier function and natural moisturising factor (NMF) levels in atopic dermatitis and healthy volunteers with known filaggrin genotype.
We investigated associations with known AD risk factors, including FLG null mutations, 23 other established AD-genetic risk variants, and atopic comorbidity.
Reported studies on the possible association of mutations in the filaggrin gene (FLG) and data on human tissue kallikreins (KLKs) and AD have been addressed.
In multivariate prognostic models, persistent PSE (eczema at 1, 2 and 4 years of age) (odds ratio 0.27 (95% confidence interval 0.18-0.41)), PSE with sleep disturbance (due to itch at least once a week at 1, 2 and/or 4 years of age) (0.59 (0.43-0.81)), parental allergy (0.73 (0.55-0.96)), parental smoking at child's birth (0.70 (0.50-0.99)) and filaggrin mutation (R501X, R2447X, 2282del4) (0.47 (0.26-0.85)) were inversely associated with complete remission by school age.
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).
Loss-of-function mutations found within the FLG gene encoding the structural protein, filaggrin, represent the most significant genetic factor predisposing to AD identified to date.
The results suggest that Raman spectroscopy and statistical analysis such as PCA could be used as an early detection procedure for FLG -related AD and as a possible quantitative marker for FLG gene mutations.
This study was designed to engineer a functional filaggrin (FLG) monomer linked to a cell-penetrating peptide (RMR) and to test the ability of this peptide to penetrate epidermal tissue as a therapeutic strategy for genetically determined atopic dermatitis (AD).
Loss-of-function mutations in filaggrin gene (FLG; OMIM #135940) have been reported to cause the semi-dominant keratinizing disorders such as ichthyosis vulgaris (IV; OMIM #146700) and atopic dermatitis (AD; OMIM #605803).
In Manchester (n = 503) an independent and significant association of the development of eczema by age 12 mo with FLG genotype was confirmed (HR 1.95, 95% CI 1.13-3.36, p = 0.02).
We found that earlier age of AD onset (P < 0.05), tendency to respiratory atopy (P = 0.03), more severe clinical characteristics of AD (higher Eczema Area and Severity Index, P = 0.02) and decrease in skin hydration (P = 0.04) were associated with FLG-related AD.
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.
The recent identification of a murine model for FLG-AD, with the detection of a homozygous frame-shift mutation in the Flg gene in flaky-tail (ft/ft) mice, stands to rapidly accelerate our understanding of mechanisms and therapeutic intervention points in AD.
The associations between FLG mutations and atopic sensitization, rhinitis and asthma are weaker than between FLG mutations and eczema, especially if those who also have eczema are excluded.