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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Natural moisturizing factor components in the stratum corneum as biomarkers of filaggrin genotype: evaluation of minimally invasive methods.

BACKGROUND: The carriers of loss-of-function mutations in the filaggrin gene (FLG) have reduced levels of natural moisturizing factor (NMF) in the stratum corneum. The concentration of NMF components which are formed by filaggrin protein breakdown in the stratum corneum might therefore be useful as a biomarker of the FLG genotype. OBJECTIVES To investigate the feasibility of different sampling methods for the determination of two NMF components, 2-pyrrolidone-5-carboxylic acid (PCA) and urocanic acid (UCA), in the stratum corneum as biomarkers for the FLG genotype. METHODS: PCA and UCA from the stratum corneum were sampled by using a tape stripping technique and an extraction technique using skin patches containing potassium hydroxide (KOH). The concentrations of PCA and UCA were measured by high-performance liquid chromatography. Eleven carriers of an FLG mutation and 10 individuals wild type for the two most common FLG mutations (R501X and R2447X) [corrected] were included in the study. RESULTS: The most significant difference between the FLG genotypes was found for PCA sampled by the tape stripping technique. The mean values of PCA obtained by the tape stripping technique were, respectively, 0.18, 0.50 and 1.64 mmol g(-1) protein in homozygous (or compound heterozygous), heterozygous and wild-type genotypes (P < 0.005 homozygous vs. heterozygous; P < 0.0001 heterozygous vs. wild type). The tape stripping technique showed less intrasubject variation compared with the KOH patches, in particular when the concentrations of UCA and PCA on the tape strips were normalized for protein amount. CONCLUSIONS: The concentration of PCA in the stratum corneum collected by tape stripping showed it to be a feasible biomarker of the FLG genotype.[1]


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