title: Nickel reactivity and filaggrin null mutations--evaluation of the filaggrin bypass theory in a general population.
abstract: BACKGROUND
  It was recently shown that filaggrin null mutation carrier status was associated with nickel allergy and self-reported intolerance to costume jewellery. Because of the biochemical characteristics of filaggrin, it may show nickel barrier properties in the stratum corneum.
  
  
  OBJECTIVE
  To investigate whether subjects with filaggrin null mutations report nickel dermatitis at an earlier age than wild-type individuals, and to analyse whether null mutation carriers have stronger patch test reactivity to nickel sulfate than do wild-type individuals.
  
  
  METHODS
  A total of 3471 Danes (18-69 years of age) answered a questionnaire about general health, and underwent patch testing and filaggrin genotyping.
  
  
  RESULTS
  The mean number of years at risk of developing nickel dermatitis was significantly lower for the filaggrin null genotype than for the wild-type genotype when ear piercing status was considered. In positive patch test readings, the proportion of null mutants increased with increasing reaction strength.
  
  
  CONCLUSIONS
  Filaggrin null mutations may lower the age of onset of nickel dermatitis. The hypothesis that ear piercings obscure the effect of filaggrin null mutations on the development of nickel allergy in statistical analyses was supported. An association between the null genotype and increased nickel sensitivity was indicated by patch test reading and questionnaire data.
authors.affiliation: Department of Dermato-Allergology, National Allergy Research Centre, Copenhagen University Hospital Gentofte, 2900 Hellerup, Denmark. kros0023@geh.regionh.dk
authors.forename: Katrine
authors.initials: K
authors.lastname: Ross-Hansen
authors.forename: Torkil
authors.initials: T
authors.lastname: Menné
authors.forename: Jeanne D
authors.initials: JD
authors.lastname: Johansen
authors.forename: Berit C
authors.initials: BC
authors.lastname: Carlsen
authors.forename: Allan
authors.initials: A
authors.lastname: Linneberg
authors.forename: Niels H
authors.initials: NH
authors.lastname: Nielsen
authors.forename: Steen
authors.initials: S
authors.lastname: Stender
authors.forename: Michael
authors.initials: M
authors.lastname: Meldgaard
authors.forename: Pal B
authors.initials: PB
authors.lastname: Szecsi
authors.forename: Jacob P
authors.initials: JP
authors.lastname: Thyssen
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D003430:Cross-Sectional Studies; D003718:Denmark / Q000453:epidemiology; D017449:Dermatitis, Allergic Contact / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D000091344:Filaggrin Proteins; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics*; D055498:Jewelry / Q000633:toxicity; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009532:Nickel / Q000633:toxicity*; D010328:Patch Tests; D011795:Surveys and Questionnaires; D055815:Young Adult
chemical_list: C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D009532:Nickel