Filaggrin Polymorphisms and the Uptake of Chemicals through the Skin-A Human Experimental Study

Filaggrin Polymorphisms and the Uptake of Chemicals through the Skin-A Human Experimental Study

The filaggrin protein is important for skin barrier structure and function. Loss-of-function (null) mutations in the filaggrin gene may increase dermal absorption of chemicals. The objective of the study was to clarify if dermal absorption of chemicals differs depending on genotype. We performed a q...

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Bibliographic Details
Published in:Environmental health perspectives Vol. 129; no. 1; p. 17002
Main Authors: Rietz Liljedahl, Emelie, Johanson, Gunnar, Korres de Paula, Helena, Faniband, Moosa, Assarsson, Eva, Littorin, Margareta, Engfeldt, Malin, Lidén, Carola, Julander, Anneli, Wahlberg, Karin, Lindh, Christian, Broberg, Karin
Format: Journal Article
Language:English
Published: United States National Institute of Environmental Health Sciences 01-01-2021
Environmental Health Perspectives
Subjects:
Absorption
Age
Arbetsmedicin och miljömedicin
Aromatic hydrocarbons
Benzophenone
Chemicals
Copy number
Cosmetics
Cytoskeletal proteins
Dermal absorption
Dermatitis
Dosage
Environmental Health and Occupational Health
Experiments
Exposure
Filaggrin
Genetic polymorphisms
Genetic screening
Health aspects
Health Sciences
Hälsovetenskap
Lag time
Medical and Health Sciences
Medicin och hälsovetenskap
Metabolites
Mutation
Organic compounds
Pesticides
Polymerase chain reaction
Proteins
Pyrene
Rate constants
Skin
Spectrometry
Structure-function relationships
Sweden
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Summary:The filaggrin protein is important for skin barrier structure and function. Loss-of-function (null) mutations in the filaggrin gene may increase dermal absorption of chemicals. The objective of the study was to clarify if dermal absorption of chemicals differs depending on genotype. We performed a quantitative real-time polymerase chain reaction (qPCR)-based genetic screen for loss-of-function mutations ( null) in 432 volunteers from the general population in southern Sweden and identified 28 null carriers. In a dermal exposure experiment, we exposed 23 null and 31 wild-type (wt) carriers to three organic compounds common in the environment: the polycyclic aromatic hydrocarbon pyrene, the pesticide pyrimethanil, and the ultraviolet-light absorber oxybenzone. We then used liquid-chromatography mass-spectrometry to measure the concentrations of these chemicals or their metabolites in the subjects' urine over 48 h following exposure. Furthermore, we used long-range PCR to measure repeat copy number variants (CNV), and we performed population toxicokinetic analysis. Lag times for the uptake and dermal absorption rate of the chemicals differed significantly between null and wt carriers with low (20-22 repeats) and high CNV (23-24 repeats). We found a dose-dependent effect on chemical absorption with increasing lag times by increasing CNV for both pyrimethanil and pyrene, and decreasing area under the urinary excretion rate curve ( ) with increasing CNV for pyrimethanil. null carriers excreted 18% and 110% more metabolite (estimated by ) for pyrimethanil than wt carriers with low and high CNV, respectively. We conclude that genotype influences the dermal absorption of some common chemicals. Overall, null carriers were the most susceptible, with the shortest lag time and highest rate constants for skin absorption, and higher fractions of the applied dose excreted. Furthermore, our results indicate that low CNV resulted in increased dermal absorption of chemicals. https://doi.org/10.1289/EHP7310.
ISSN:0091-6765
1552-9924
1552-9924
DOI:10.1289/EHP7310