title: The nickel dose-response relationship by filaggrin genotype (FLG).
abstract: BACKGROUND
  On skin contact, nickel accumulates in the stratum corneum, where it is probably bound to proteins and amino acids. One probable contributor is filaggrin, which binds nickel avidly. Filaggrin gene (FLG) null mutations lead to a complete lack of filaggrin production from the affected allele, and have been associated with an increased risk of nickel contact sensitization in German and Danish adults.
  
  
  OBJECTIVE
  To investigate whether the experimental nickel elicitation threshold level differed between heterozygous FLG mutation and non-mutation carriers.
  
  
  METHODS
  Thirteen nickel-sensitized female patients, seven heterozygous mutation carriers and six non-mutation carriers (genotyped for R501X, 2282del4, or R2447X), were patch tested and performed a repeated open application test (ROAT) with a nickel sulfate dilution series. Logistic threshold dose-response analyses were used to test for differences between the two groups.
  
  
  RESULTS
  No difference was found in the dose-response relationship between FLG mutation and non-mutation carriers.
  
  
  CONCLUSIONS
  On the basis of this small patient study, it appears that the elicitation threshold level for nickel is independent of FLG null mutation single-allele carrier status.
authors.affiliation: Department of Dermato-Allergology, National Allergy Research Centre, Copenhagen University Hospital Gentofte, Hellerup, 2900, Denmark.
authors.forename: Katrine
authors.initials: K
authors.lastname: Ross-Hansen
authors.forename: Jeanne D
authors.initials: JD
authors.lastname: Johansen
authors.forename: Aage
authors.initials: A
authors.lastname: Vølund
authors.forename: Torkil
authors.initials: T
authors.lastname: Menné
authors.forename: Jacob P
authors.initials: JP
authors.lastname: Thyssen
mesh_terms: D000328:Adult; D000368:Aged; D003877:Dermatitis, Contact / Q000209:etiology / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D004817:Epidermis / Q000378:metabolism; D005260:Female; D000091344:Filaggrin Proteins; D005838:Genotype; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics* / Q000378:metabolism; D007509:Irritants / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D009154:Mutation; D009532:Nickel / Q000008:administration & dosage* / Q000009:adverse effects / Q000378:metabolism; D010328:Patch Tests; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D007509:Irritants; D010750:Phosphoproteins; C029938:nickel sulfate; D009532:Nickel
keywords: experimental nickel contact elicitation; filaggrin genotype