Filaggrin gene mutations and new SNPs in asthmatic patients: a cross-sectional study in a Spanish population

Abstract

BackgroundSeveral null-mutations in the FLG gene that produce a decrease or absence of filaggrin in the skin and predispose to atopic dermatitis and ichthyosis vulgaris have been described. The relationship with asthma is less clear and may be due to the influence of atopy in patients with associated asthma.MethodsFour hundred individuals were included, 300 patients diagnosed with asthma divided into two groups according to their phenotype (allergic and non-allergic asthma) and 100 strictly characterized controls. The coding region and flanking regions of the FLG gene were amplified by PCR. We proceeded to the characterization of potential gene variants in that region by RFLP and sequencing and analysed their association with lung function parameters, asthma control and severity, and quality of life.ResultsWe identified two null-mutations (R501X and 2282del4), seven SNPs previously described in databases and three SNPs that had not been previously described. One of the SNP identified in this study (1741A > T) was more frequently detected in patients with non-allergic asthma, worse FVC, FEV1 and PEF values and a higher treatment step. In addition, lowered spirometric values were observed in the non-allergic group carrying any of the nonsynonymous SNPs.ConclusionsIn the association study of genetic variants of the FLG gene in our population the 1741A > T polymorphism seems to be associated with non-allergic asthma.

Atopic dermatitis: the skin barrier and beyond

“…The defects in structural epidermal proteins outlined above collectively contribute to a dysfunctional cutaneous barrier that underlies the AD phenotype of dry, inflamed skin, and also serves as a site for allergic sensitization to antigens. Indeed, FLG mutations have been reported to be associated with atopic asthma, allergic rhinitis, nickel allergy and food allergy, suggesting that FLG mutation‐associated stratum corneum barrier defects lead to increased percutaneous allergen exposure. Apart from in one recent and relatively small study, FLG mutations have not been associated with asthma without AD, and most of the identified asthma‐associated genes are not associated with AD, suggesting that atopic asthma is a distinct subentity .…”

Evidence for the critical role of the PI3K signaling pathway in particulate matter-induced dysregulation of the inflammatory mediators COX-2/PGE2 and the associated epithelial barrier protein Filaggrin in the bronchial epithelium

“…Filaggrin belongs to the keratin gene family and is involved in the differentiation of epithelial cells (Zhong et al 2005 ). The loss-of-function in mutations of FLG in humans is correlated with airway hyperresponsiveness, a characteristic of PM-related airway disease (Berg et al 2012 ; Cubero et al 2016 ; Palmer et al 2007 ). A systemic review of the literature concerning COX-2 and Filaggrin pointed out that PM downregulates Filaggrin via COX-2 expression/PGE 2 production, leading to skin barrier dysfunction (Lee et al 2016 ).…”

Prevalence of FLG loss‐of‐function mutations R501X, 2282del4, and R2447X in Spanish children with atopic dermatitis

“…Only 1 study has assessed the prevalence of FLG mutations in a Spanish population, specifically in a cohort of asthma patients and a corresponding control group . That study revealed frequencies of 2% and 1% for R501X and 2282del4, respectively, in the control group, and lower frequencies in the asthma cohort (1% and absent, respectively).…”