title: Filaggrin loss-of-function mutations are associated with food allergy in childhood and adolescence.
abstract: BACKGROUND
  Filaggrin is an epidermal protein that has a role in skin barrier function. Filaggrin loss-of-function (FLG-LOF) mutations are a significant risk factor for eczema and atopy, but their association with food allergy (FA) is less clear.
  
  
  OBJECTIVE
  We explored the longitudinal relationship between 3 common FLG-LOF mutations and FA using the Isle of Wight birth cohort.
  
  
  METHODS
  FA diagnosis was based on recognized allergic reactions within 4 hours after exposure to known food allergens. Food allergen sensitization (FAS) was identified by using skin prick tests conducted between 1 and 18 years of age to a range of food allergens. Three FLG mutations were genotyped in 1150 (79%) of 1456 children. The temporal relationships between FA, FAS, and eczema in children with FLG mutations were explored by using path analysis with total, direct, and indirect effect models.
  
  
  RESULTS
  There was a significant total effect of FLG-LOF mutations on the risk of FA in later childhood at the ages of 10 (odds ratio, 31.46; 95% CI, 2.86 to >100) and 18 (odds ratio, 4.25; 95% CI, 1.55-11.61) years. Path analysis showed that there was no direct effect of FLG-LOF mutations on FA at any age; however, an indirect effect was found on FA at all ages through eczema and FAS in the earlier years.
  
  
  CONCLUSIONS
  FLG-LOF mutations are associated with FA in older children through eczema and FAS during early childhood. Our results highlight a biologically plausible pathway, which suggests that skin barrier function is important in the development and persistence of FA.
authors.affiliation: University of Southampton, Faculty of Medicine, Southampton, United Kingdom; James Cook University Hospital, Middlesbrough, United Kingdom.
authors.forename: Devasmitha
authors.initials: D
authors.lastname: Venkataraman
authors.affiliation: Division of Epidemiology, Biostatistics, and Environmental Health, School of Public Health, University of Memphis, Memphis, Tenn.
authors.forename: Nelís
authors.initials: N
authors.lastname: Soto-Ramírez
authors.affiliation: David Hide Asthma and Allergy Research Centre, Isle of Wight, United Kingdom; University Hospitals Southampton NHS Foundation Trust, Southampton, United Kingdom.
authors.forename: Ramesh J
authors.initials: RJ
authors.lastname: Kurukulaaratchy
authors.affiliation: Clinical and Experimental Sciences, University of Southampton, Southampton, United Kingdom; Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
authors.forename: John W
authors.initials: JW
authors.lastname: Holloway
authors.affiliation: Division of Epidemiology, Biostatistics, and Environmental Health, School of Public Health, University of Memphis, Memphis, Tenn.
authors.forename: Wilfried
authors.initials: W
authors.lastname: Karmaus
authors.affiliation: College of Veterinary Medicine, Michigan State University, East Lansing, Mich.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Ewart
authors.affiliation: David Hide Asthma and Allergy Research Centre, Isle of Wight, United Kingdom; University Hospitals Southampton NHS Foundation Trust, Southampton, United Kingdom; Clinical and Experimental Sciences, University of Southampton, Southampton, United Kingdom. Electronic address: S.H.Arshad@soton.ac.uk.
authors.forename: S Hasan
authors.initials: SH
authors.lastname: Arshad
authors.affiliation: University Hospitals Southampton NHS Foundation Trust, Southampton, United Kingdom; Clinical and Experimental Sciences, University of Southampton, Southampton, United Kingdom.
authors.forename: Mich
authors.initials: M
authors.lastname: Erlewyn-Lajeunesse
mesh_terms: D000293:Adolescent; D000485:Allergens / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D000091344:Filaggrin Proteins; D005500:Follow-Up Studies; D005512:Food Hypersensitivity / Q000235:genetics / Q000276:immunology*; D005838:Genotype; D006801:Humans; D007223:Infant; D007381:Intermediate Filament Proteins / Q000235:genetics*; D008297:Male; D009154:Mutation / Q000235:genetics; D012867:Skin / Q000276:immunology*; D006113:United Kingdom
chemical_list: D000485:Allergens; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins
keywords: FLG-LOF; Food allergy; eczema; filaggrin; food allergen sensitization; path analysis; prediction