title: Association of filaggrin variants with asthma and rhinitis: is eczema or allergic sensitization status an effect modifier?
abstract: BACKGROUND
  Associations of variants of the filaggrin gene, i.e. FLG with asthma and rhinitis have been shown to be modulated by eczema status. However, it is unknown whether allergic sensitization status modifies this association. The aim of this study was to determine whether FLG variants need eczema and/or allergic sensitization as a necessary component to execute adverse effects on coexisting and subsequent asthma and rhinitis.
  
  
  METHODS
  In the Isle of Wight birth cohort, repeated measurements of asthma, rhinitis, eczema and allergic sensitization (documented by skin-prick tests) were taken in 1,456 children at the ages of 1, 2, 4, 10 and 18 years. Filaggrin haploinsufficiency was defined as having at least the minor allele of R501X, 2282del4 or S3247X variants. log-binomial regression models were used to test associations and statistical interactions.
  
  
  RESULTS
  FLG variants increased the risk of asthma [risk ratio (RR) 1.39, 95% confidence interval (CI) 1.06-1.80] and rhinitis (RR 1.37, 95% CI 1.16-1.63). In the delayed-effects models, 'FLG variants plus allergic sensitization' and 'FLG variants plus eczema' increased the risk of subsequent asthma by 4.93-fold (95% CI 3.61-6.71) and 3.33-fold (95% CI 2.45-4.51), respectively, during the first 18 years of life. In contrast, neither eczema nor allergic sensitization in combination with FLG variants increased the risk of later rhinitis.
  
  
  CONCLUSIONS
  Allergic sensitization and eczema modulated the association between FLG variants and asthma but not rhinitis. Our results imply that the mechanisms and pathways through which FLG variants predispose to an increased risk of asthma and rhinitis may be different.
authors.affiliation: Department of Epidemiology and Biostatistics, Norman J. Arnold School of Public Health, University of South Carolina, Columbia, S.C., USA.
authors.forename: Ali H
authors.initials: AH
authors.lastname: Ziyab
authors.forename: Wilfried
authors.initials: W
authors.lastname: Karmaus
authors.forename: Hongmei
authors.initials: H
authors.lastname: Zhang
authors.forename: John W
authors.initials: JW
authors.lastname: Holloway
authors.forename: Susan E
authors.initials: SE
authors.lastname: Steck
authors.forename: Susan
authors.initials: S
authors.lastname: Ewart
authors.forename: Syed Hasan
authors.initials: SH
authors.lastname: Arshad
mesh_terms: D000293:Adolescent; D001249:Asthma / Q000209:etiology* / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D004485:Eczema / Q000150:complications*; D015987:Effect Modifier, Epidemiologic; D005260:Female; D000091344:Filaggrin Proteins; D005500:Follow-Up Studies; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D060005:Genotyping Techniques; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000150:complications* / Q000175:diagnosis; D007223:Infant; D007381:Intermediate Filament Proteins / Q000235:genetics*; D008297:Male; D011446:Prospective Studies; D012220:Rhinitis / Q000209:etiology* / Q000235:genetics; D012882:Skin Tests
chemical_list: C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D005819:Genetic Markers; D007381:Intermediate Filament Proteins