Filaggrin Gene Defects Are Independent Risk Factors for Atopic Asthma in a Polish Population: A Study in ECAP Cohort

Abstract

Background FLG null variants of which 2282del4 and R501X are the most frequent in Caucasians are established risk factors for atopic dermatitis (AD) with an effect probably mediated through impairment of epidermal barrier. Among subjects with AD FLG defects are also consistently associated with asthma and allergic rhinitis (AR) but it is less clear to what extent these associations are also present independently from skin disease. The aim of the present study was to evaluate the role of 2282del4 and R501X in predisposing to these allergic phenotypes in a Polish population.Methodology2282del4 and R501X were typed among 3,802 participants of the Epidemiology of Allergic Diseases in Poland (ECAP) survey, a cross-sectional population-based study using ECRHS II and ISAAC questionnaires, and ambulatory examination.Principal FindingsThe FLG null variants were associated with AD (OR = 2.01, CI: 1.20–3.36, P = 0.007), allergic rhinitis (in particular persistent form, OR = 1.69, CI:1.12–2.54, P = 0.011), and asthma (in particular atopic asthma, OR = 2.22, CI:1.24–3.96, P = 0.006). Association with atopic asthma (but not persistent allergic rhinitis) was also present in the absence of AD, (OR = 2.02, CI: 1.07–3.81, P = 0.027) as well as in the absence of AD and history of broadly defined inflammatory skin disease (OR = 2.30, CI: 1.07–4.93, P = 0.03). Association to atopic asthma would have not been found if diagnosis was made by questionnaire only (OR = 1.15, CI: 0.58–2.32, P = 0.8). We did not observe an association between FLG variants and allergic sensitizations (P = 0.8) or total IgE. (P = 0.6).Conclusions/SignificanceIn a Polish population FLG 2282del4 and R501X carriage increases risk for development of AD and atopic asthma (also in the absence of AD or history thereof). This suggests that interventions aimed at restoring epidermal barrier may have a general role in asthma prophylaxis/treatment.

Filaggrin loss-of-function mutations as a predictor for atopic eczema, allergic sensitization and eczema-associated asthma in Polish children population

“…Although the potential role of FLG mutations as a major predisposing factor for atopic eczema has received considerable attention in recent years, to date there were only two studies investigating FLG mutations R501X, 2282del4 in Polish adults and older children. 15,16 In our results, we found a significant association between the combined genotype of all 4 FLG mutations and the susceptibility to eczema. The frequency of 2282del14 deletion showed a similar trend, although the statistical significance of this association was borderline.…”

Lelp-1, Its Role in Atopic Dermatitis and Asthma: Poland and Portugal

“…Other authors [35], refer a correlation of log10 serum IgE levels and rs7534334 in a group of asthmatic patients being the mutant genotype (TT) in patients, those with higher levels of IgE comparing with controls (TT) and comparing with wild type genotype (CC) in patients (3.49 ± 0.91 vs 2.43 ± 0.52 vs 2.92 ± 0.59) .This point to the works who showed that when skin barrier function is compromised even without skin disease there is an increased incidence of atopic disease [28].…”

“…This barrier defect could be present even in the absence of eczema [26,28,33,47], which could help us to understand the physiopathology of AD associated with LELP1 polymorphism [rs7534334] and other polymorphisms located on genes of EDC complex.…”

“…contributions to abnormalities in respective immune and barrier phenotypes have been highlighted recently in lesional and nonlesional AD skin [28].…”

Flaky Tail Mouse as a Novel Animal Model of Atopic Dermatitis: Possible Roles of Filaggrin in the Development of Atopic Dermatitis

“…The association of FLG mutation with atopic march has been reported in cases involving pediatric asthma (Muller, et al, 2009), peanut allergy (Brown, et al, 2011), atopic asthma (Poninska, et al, 2011), allergic rhinitis (Poninska, et al, 2011) and nickel allergy (Novak, et al, 2008). In addition, epidemiological studies have identified extremely significant statistical association between FLG mutation and AD.…”