title: Filaggrin null mutations are associated with increased asthma exacerbations in children and young adults.
abstract: BACKGROUND
  Filaggrin (FLG) null mutations are important genetic predisposing factors for atopic asthma and have recently been shown to influence controller and reliever medication needs in asthmatic children. Our objective was to study the role of FLG null alleles in asthma exacerbations.
  
  
  METHODS
  FLG mutations R501X and 2282del4 were assayed in 1135 individuals ranging from 3 to 22 years old with asthma from Tayside and Dumfries, Scotland. Asthma exacerbations over the previous 6 months were also studied.
  
  
  RESULTS
  The FLG mutations were significantly associated with greater risk of exacerbations in children with asthma. Exacerbations were significant for the R501X but not the 2282del4 mutation and the combined genotype compared to the wild-type with odds ratios of 1.97 (95% CI, 1.19-3.22; P = 0.009) and 1.61 (95% CI, 1.08-2.40; P = 0.021), respectively. Individuals with FLG null alleles were more likely to require oral steroids (31.4%vs 19.5%; OR = 1.89; P = 0.021) for their exacerbations. There was also a 1.71-fold increased risk (42.6%vs 30%; P = 0.041) of school absence owing to asthma exacerbations in asthmatic individuals with FLG null mutation. On sub-group analysis, the effect of FLG mutations on asthma exacerbations is significant (P = 0.045) only for participants with relatively mild asthma controlled on inhaled steroids, with inhaled albuterol according to need.
  
  
  CONCLUSIONS
  In addition to their effect on asthma medication requirements reported previously, there is an association between the presence of FLG null mutations and the risk of asthma exacerbations in asthmatic children and young adults.
authors.affiliation: Maternal and Child Health Sciences, Ninewells Hospital and Medical School, Dundee, UK.
authors.forename: K
authors.initials: K
authors.lastname: Basu
authors.forename: C N A
authors.initials: CN
authors.lastname: Palmer
authors.forename: B J
authors.initials: BJ
authors.lastname: Lipworth
authors.forename: W H Irwin
authors.initials: WH
authors.lastname: McLean
authors.forename: A
authors.initials: A
authors.lastname: Terron-Kwiatkowski
authors.forename: Y
authors.initials: Y
authors.lastname: Zhao
authors.forename: H
authors.initials: H
authors.lastname: Liao
authors.forename: F J D
authors.initials: FJ
authors.lastname: Smith
authors.forename: A
authors.initials: A
authors.lastname: Mitra
authors.forename: S
authors.initials: S
authors.lastname: Mukhopadhyay
mesh_terms: D000293:Adolescent; D001249:Asthma / Q000188:drug therapy* / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D000091344:Filaggrin Proteins; D005938:Glucocorticoids / Q000008:administration & dosage*; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics*; D008297:Male; D009154:Mutation; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D005938:Glucocorticoids; D007381:Intermediate Filament Proteins