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

被引:131
作者
Kezic, S. [1 ]
Kammeyer, A. [2 ]
Calkoen, F. [1 ]
Fluhr, J. W. [3 ,4 ]
Bos, J. D. [2 ]
机构
[1] Univ Amsterdam, Acad Med Ctr, Coronel Inst Occupat Hlth, NL-1100 DE Amsterdam, Netherlands
[2] Univ Amsterdam, Acad Med Ctr, Dept Dermatol, NL-1100 DE Amsterdam, Netherlands
[3] Bioskin, Berlin, Germany
[4] Charite, Dept Dermatol & Allergol, Ctr Expt Appl Cutaneous Physiol, D-13353 Berlin, Germany
关键词
2-pyrrolidone-5-carboxylic acid; FLG gene mutations; natural moisturizing factor; urocanic acid; UROCANIC ACID ISOMERS; PYRROLIDONE CARBOXYLIC-ACID; ATOPIC-DERMATITIS; IN-VIVO; HISTIDINE; GENE; SKIN; MUTATIONS; PROTEINS; WATER;
D O I
10.1111/j.1365-2133.2009.09342.x
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
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 2282del4) 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.
引用
收藏
页码:1098 / 1104
页数:7
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