Low frequency of filaggrin null mutations in Croatia and their relation with allergic diseases

Abstract

Filaggrin gene (FLG) null mutations are considered associated with atopic dermatitis. This study was conducted to determine the prevalence of FLG null mutations R501X, 2282del4, R2447X and S3247X in the Croatian population and their role in the occurrence of allergic diseases including atopic dermatitis, allergic rhinitis, asthma and allergic contact dermatitis (ACD). Study enrolled 440 freshmen with defined allergic diseases by means of both present symptoms in International Study of Asthma and Allergies in Childhood questionnaire (relevant respiratory and/or skin symptoms) and markers of allergic sensitization (positive skin prick and/or patch test). FLG null mutations were successfully genotyped in 423 students of which 11 (2.6%) were carriers of FLG null mutation: 1/423 (0.2%) was heterozygous for R501X and 10/423 (2.4%) were heterozygous for 2282del4. No carriers of R2447X and S3247X mutations were identified. In wild-type FLG carriers (412 subjects), atopic dermatitis was present in 45 (11%), allergic rhinitis in 70 (17%) and allergic asthma in 29 (7%) students. Twenty-five of 393 (7%) patch-tested wild-type FLG carriers had ACD. Among 11 FLG null mutation carriers, four had one or more allergic diseases, and five had reported skin symptoms without defined allergic sensitization (positive skin prick test and/or patch test). FLG null mutations were not confirmed as a predictor of analysed allergic diseases, but were confirmed as an independent predictor of skin symptoms (OR 17.19, 95% CI 3.41-86.6, P < 0.001). Our results in general indicate a low frequency of FLG null mutations in the studied Croatian population supporting a theory of a latitude-dependent distribution of FGL null mutations in Europe, with a decreasing north-south gradient of R501X and 2282del4 mutation frequency. The relation between FLG null mutations and skin disorders was confirmed.

Skin health and safety at work in Croatian hairdressing apprentices

“…It can be speculated that population-specific individual risk factors may contribute to this difference. Notably, the prevalence of filaggrin null mutations, which constitute a recognized susceptibility factor for the development of irritant contact dermatitis (3), differs significantly between populations, with a marked decrease from northern to southern Europe (28)(29)(30)(31)(32). The low prevalence of filaggrin null mutations found in Croatia (28) may render our cohort of apprentices less prone to irritant skin changes, and it would be worth testing this hypothesis in further epidemiological studies.…”

Occupational and Non-Occupational Allergic Contact Dermatitis: A Follow-Up Study

“…However, our previous study revealed a low frequency of common FLG null mutations in the Croatian population, suggesting that these mutations do not have a significant impact on the development and course of skin diseases, including ACD, in the Croatian and other populations with low penetrations of FLG mutations [38]. The data indicate a decreasing north-south gradient of R501X and 2282del4 FLG mutation frequencies in Europe with a lower penetration of FLG mutations in the Italian and Croatian population when compared to Ireland, the UK and Germany [38,39,40]. The results of the present study are in line with these suggestions.…”

Associations of TNFα <b><i>-308G>A</i></b>, TNFα <b><i>-238G>A</i></b>,<b> </b>IL-1α <b><i>-889C>T</i></b> and IL-10 <b><i>-1082G>A </i></b>Genetic Polymorphisms with Atopic Diseases: Asthma, Rhinitis and Dermatitis

“…The number of responders was 440, and for the purpose of this study 437 participants from whom buccal swabs were collected [55] were recontacted by phone in 2014 and asked to accept via mail a consent form for this study, i.e. consent for the analysis of additional cytokine polymorphisms from their buccal swabs.…”