title: 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.
  
  
  METHODS
  2282del4 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.
  
  
  RESULTS
  The 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
  In 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.
authors.affiliation: Department of Medical Genetics, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Ponińska
authors.forename: Bolesław
authors.initials: B
authors.lastname: Samoliński
authors.forename: Aneta
authors.initials: A
authors.lastname: Tomaszewska
authors.forename: Filip
authors.initials: F
authors.lastname: Raciborski
authors.forename: Piotr
authors.initials: P
authors.lastname: Samel-Kowalik
authors.forename: Artur
authors.initials: A
authors.lastname: Walkiewicz
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Lipiec
authors.forename: Barbara
authors.initials: B
authors.lastname: Piekarska
authors.forename: Jarosław
authors.initials: J
authors.lastname: Komorowski
authors.forename: Edyta
authors.initials: E
authors.lastname: Krzych-Fałta
authors.forename: Andrzej
authors.initials: A
authors.lastname: Namysłowski
authors.forename: Jacek
authors.initials: J
authors.lastname: Borowicz
authors.forename: Grażyna
authors.initials: G
authors.lastname: Kostrzewa
authors.forename: Sławomir
authors.initials: S
authors.lastname: Majewski
authors.forename: Rafał
authors.initials: R
authors.lastname: Płoski
mesh_terms: D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000235:genetics*; D002648:Child; D015331:Cohort Studies; D003876:Dermatitis, Atopic / Q000235:genetics; D005062:European Union; D000091344:Filaggrin Proteins; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005828:Genetics, Population; D055106:Genome-Wide Association Study; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics*; D015337:Multicenter Studies as Topic; D020125:Mutation, Missense / Q000502:physiology; D011044:Poland; D011110:Polymorphism, Genetic; D012307:Risk Factors; D017384:Sequence Deletion / Q000502:physiology; D055815:Young Adult
chemical_list: C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins