| Description: |
Why did you do this work? Atopic dermatitis (AD), asthma, food allergy and allergic rhinitis are conditions with a significant disease burden in childhood. Their aetiology, however, is poorly understood. The skin-barrier hypothesis is well-understood, in which the skin acts as a barrier to provide protection from external physical and chemical insults and from allergens. A defective skin barrier can cause sensitization and subsequent development of one or more allergy-related conditions. We therefore sought to investigate the role of genes associated with skin barrier dysfunction on childhood allergy. What did you do? We conducted a systematic review and meta-analysis of the effects of variation in skin-barrier-related genes on childhood allergy-related conditions (registered on PROSPERO; CRD42022355771). A systematic search strategy was used to interrogate Embase, MEDLINE, Emcare, CINAHL and CENTRAL databases, yielding 6018 abstracts. Following abstract screening, 941 full texts were screened using predefined inclusion and exclusion criteria [ table 1 ]. Only reports on genes related to skin-barrier function, identified by the GeneOntology Skin Barrier database, 6 were included. Sixty full texts fulfilled the above criteria and were included in the systematic review. Quality assessment was performed for all included full texts, utilizing the validated Quality of Genetic Studies (Q-GENIE) tool. 7 Data extraction was performed and data was grouped according to study type and allergic condition. All processes described were conducted by two independent reviewers. What did you find? All included papers (n=60) related to the filaggrin gene ( FLG ). Meta-analysis was performed on results from 28 papers using Stata-BE statistical software. Remaining papers (n= 32) were assessed by narrative synthesis. We explored associations between FLG variation and atopic dermatitis in cohort [OR 2.43, 95%CI 1.89–3.10; n=13] and case-control [OR 4.44, 95%CI 2.42 – 8.12; n=7] studies. FLG variation was also associated with asthma in ... |