title: Interaction between filaggrin null mutations and tobacco smoking in relation to asthma.
abstract: BACKGROUND
  The mechanisms underlying the association between filaggrin (FLG) deficiency and asthma are not known. It has been hypothesized that FLG deficiency leads to enhanced percutaneous exposure to environmental substances that might trigger immune responses. We hypothesized that interactions between FLG deficiency and environmental exposures play a role in asthma development.
  
  
  OBJECTIVE
  We sought to investigate possible interactions between FLG null mutations and tobacco smoking in relation to asthma.
  
  
  METHODS
  A total of 3471 adults from a general population sample participated in a health examination. Lung function and serum specific IgE levels to inhalant allergens were measured, and information on asthma and smoking was obtained by means of questionnaire. Participants were genotyped for the 2 most common FLG null mutations in white subjects: R501X and 2282del4. Another Danish population was used for replication.
  
  
  RESULTS
  The FLG null mutation genotype was significantly associated with a higher prevalence of asthma and decreased FEV(1)/forced vital capacity ratio. In logistic regression analyses with asthma as the outcome, a significant interaction was found between FLG null mutations and smoking status (P = .02). This interaction was confirmed, although it was not statistically significant, in another Danish population study. Interactions between FLG genotype and cumulated smoking exposure were found in relation to asthma (P = .03) and decreased FEV(1)/forced vital capacity ratio (P = .03). A 3-way interaction was found among FLG genotype, smoking, and asthma, suggesting that the FLG-smoking interaction mainly played a role in nonatopic subjects.
  
  
  CONCLUSIONS
  FLG null mutations modified the effects of smoking on the risk of asthma. This finding might have implications for risk stratification of the population.
authors.affiliation: Research Centre for Prevention and Health, Glostrup University Hospital, the Capital Region of Denmark, Glostrup, Denmark.
authors.forename: Nikolaj Drimer
authors.initials: ND
authors.lastname: Berg
authors.forename: Lise Lotte N
authors.initials: LL
authors.lastname: Husemoen
authors.forename: Betina Heinsbæk
authors.initials: BH
authors.lastname: Thuesen
authors.forename: Lars-Georg
authors.initials: LG
authors.lastname: Hersoug
authors.forename: Jesper
authors.initials: J
authors.lastname: Elberling
authors.forename: Jacob Pontoppidan
authors.initials: JP
authors.lastname: Thyssen
authors.forename: Berit Christina
authors.initials: BC
authors.lastname: Carlsen
authors.forename: Jeanne Duus
authors.initials: JD
authors.lastname: Johansen
authors.forename: Torkil
authors.initials: T
authors.lastname: Menné
authors.forename: Klaus
authors.initials: K
authors.lastname: Bønnelykke
authors.forename: Steen
authors.initials: S
authors.lastname: Stender
authors.forename: Michael
authors.initials: M
authors.lastname: Meldgaard
authors.forename: Pal Bela
authors.initials: PB
authors.lastname: Szecsi
authors.forename: Allan
authors.initials: A
authors.lastname: Linneberg
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001249:Asthma / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D017449:Dermatitis, Allergic Contact / Q000097:blood / Q000235:genetics / Q000503:physiopathology; D005260:Female; D000091344:Filaggrin Proteins; D005838:Genotype; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000097:blood / Q000235:genetics / Q000503:physiopathology; D007073:Immunoglobulin E / Q000097:blood; D007381:Intermediate Filament Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012907:Smoking / Q000235:genetics*; D013147:Spirometry; D055815:Young Adult
chemical_list: C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D007073:Immunoglobulin E