title: Association between loss-of-function mutations in the filaggrin gene and self-reported food allergy and alcohol sensitivity.
abstract: BACKGROUND
  Loss-of-function mutations of the filaggrin (FLG) gene cause an impaired skin barrier and increase the risk of atopic dermatitis. Interestingly, FLG mutations have also been found to be associated with a high risk of peanut allergy.
  
  
  OBJECTIVE
  We investigated the association of FLG mutations with self-reported food allergy, symptoms of oral allergy syndrome (OAS), and alcohol sensitivity.
  
  
  METHODS
  A total of 3,471 adults from the general population participated in a health examination. Information on food allergies, OAS and alcohol sensitivity was obtained by questionnaire. FLG mutation carriers were defined as having at least one null mutation allele of R501X or 2282del4. Primary lactose intolerance (PLI) was defined as the C/C genotype of the rs4988235 polymorphism.
  
  
  RESULTS
  FLG mutations were associated with a higher risk of self-reported allergy to eggs (OR 3.22 and 95% CI 1.46-7.11), milk (OR 2.10 and 95% CI 1.12-3.92), fish (OR 4.54 and 95% CI 1.88-10.96) and wheat (OR 3.59 and 95% CI 1.61-8.02), but not with symptoms of OAS (OR 1.05 and 95% CI 0.73-1.51). Serum-specific IgE was measured in a subsample and confirmed the association between FLG and IgE to milk. A significant gene-by-gene interaction between FLG and PLI was observed in relation to self-reported allergy to milk. Furthermore, FLG mutations were associated with a higher risk of alcohol sensitivity.
  
  
  CONCLUSIONS
  We found that loss-of-function mutations in the FLG gene were significantly associated with self-reported food allergy and alcohol sensitivity, but not with OAS. These findings, if confirmed, support the idea that skin barrier functions may be involved in the pathogenesis of food allergy.
authors.affiliation: Research Centre for Prevention and Health, Glostrup University Hospital, Glostrup, Denmark. alllin01 @ regionh.dk
authors.forename: Allan
authors.initials: A
authors.lastname: Linneberg
authors.forename: Runa V
authors.initials: RV
authors.lastname: Fenger
authors.forename: Lise-Lotte N
authors.initials: LL
authors.lastname: Husemoen
authors.forename: Betina H
authors.initials: BH
authors.lastname: Thuesen
authors.forename: Tea
authors.initials: T
authors.lastname: Skaaby
authors.forename: Arturo
authors.initials: A
authors.lastname: Gonzalez-Quintela
authors.forename: Carmen
authors.initials: C
authors.lastname: Vidal
authors.forename: Berit C
authors.initials: BC
authors.lastname: Carlsen
authors.forename: Jeanne D
authors.initials: JD
authors.lastname: Johansen
authors.forename: Torkil
authors.initials: T
authors.lastname: Menné
authors.forename: Steen
authors.initials: S
authors.lastname: Stender
authors.forename: Michael
authors.initials: M
authors.lastname: Melgaard
authors.forename: Pal B
authors.initials: PB
authors.lastname: Szecsi
authors.forename: Nikolaj D
authors.initials: ND
authors.lastname: Berg
authors.forename: Jacob P
authors.initials: JP
authors.lastname: Thyssen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000428:Alcohol Drinking / Q000235:genetics*; D004327:Drinking Behavior; D005260:Female; D000091344:Filaggrin Proteins; D020022:Genetic Predisposition to Disease; D006801:Humans; D006967:Hypersensitivity / Q000235:genetics*; D007381:Intermediate Filament Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D021183:Peanut Hypersensitivity / Q000235:genetics; D011795:Surveys and Questionnaires
chemical_list: C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins