The nickel dose–response relationship by filaggrin genotype (FLG)

Abstract

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. To investigate whether the experimental nickel elicitation threshold level differed between heterozygous FLG mutation and non-mutation carriers. 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. No difference was found in the dose-response relationship between FLG mutation and non-mutation carriers. 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.