MedicalResearch.com Interview with:
Dr. Alan Irvine, MD
Professor in Dermatology
Department of Clinical Medicine
Trinity College Dublin
Medical Research: What is the background for this study? What are the main findings?
Response: Atopic diseases include atopic dermatitis (AD, also know as eczema), food allergy, allergic rhinitis and asthma. The prevalence of these diseases has increased in recent decades causing considerable morbidity in childhood. The putative “Atopic March” refers to the typical sequence of clinical manifestation of atopic disease, usually initiated by atopic dermatitis from early infancy.
Parental atopy is an independent risk factor for development of
atopic disease. The genetic mechanisms and inheritance pattern of atopic diseases are not fully elucidated but recent candidate gene studies and Genome Wide Association Studies (GWAS) have yielded some insights. The most widely replicated and most significant gene to influence atopic dermatitis is Filaggrin (
FLG). Filaggrin is a filament binding protein in the stratum Corneum.
FLG loss-of-function mutations (
FLG mut) occur in 10% of Europeans, imparting an increased risk of atopic dermatitis, food allergy and asthma. The overall increase in risk of atopic dermatitis conferred by a single
FLG loss-of-function mutation is approximately 3.3, with a significant additional and independent effect conferred by intragenic copy number variations in
FLG. Importantly
FLG mutations increase the risk of developing asthma only in the presence of atopic dermatitis.
While loss-of-function mutations in the skin barrier protein
filaggrin (
FLG) are a major risk for atopic dermatitis, the pathogenic sequence of disturbances in skin barrier function prior to or during the early development of atopic dermatitis is not fully understood. A more detailed understanding of these events is needed to develop a clearer picture of disease pathogenesis. A robust, non-invasive test to identify babies at high risk of atopic dermatitis would be important in planning early intervention and/or prevention studies.
We found that raised transepidermal water loss at birth and at two months in asymptomatic infants predates the development of atopic dermatitis. This signal is independent of
FLG status and parental atopy.
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