US EPA

5674345 

Journal Article 

Associations of filaggrin gene loss-of-function variants with urinary phthalate metabolites and testicular function in young Danish men 

Joensen, UN; Jørgensen, N; Meldgaard, M; Frederiksen, H; Andersson, AM; Menné, T; Johansen, JD; Carlsen, BC; Stender, S; Szecsi, PB; Skakkebæk, NE; Rajpert-De Meyts, E; Thyssen, JP 

2014 

Yes 

Environmental Health Perspectives
ISSN: 0091-6765
EISSN: 1552-9924 

122 

4 

345-350 

English 

24380925 

DOI:10.1289/ehp.1306720 

WOS:000334069100016 

https://search.proquest.com/docview/1661375882?accountid=171501
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Background: Filaggrin is an epidermal protein that is crucial for skin barrier function. Up to 10% of Europeans and 5% of Asians carry at least one null allele in the filaggrin gene (FLG). Reduced expression of filaggrin in carriers of the null allele is associated with facilitated transfer of allergens across the epidermis. We hypothesized that these individuals may have increased transdermal uptake of endocrine disruptors, including phthalates. Objectives: We investigated urinary excretion of phthalate metabolites and testicular function in young men with and without FLG loss-of-function variants in a cross-sectional study of 861 young men from the general Danish population. Methods: All men were genotyped for FLG R501X, 2282del4, and R2447X loss-of-function variants. We measured urinary concentrations of 14 phthalate metabolites and serum levels of reproductive hormones. We also evaluated semen quality. Results: Sixty-five men (7.5%) carried at least one FLG-null allele. FLG-null carriers had significantly higher urinary concentrations of several phthalate metabolites, including a 33% higher concentration of MnBP (mono-n-butyl phthalate; 95% CI: 16, 51%). FLG-null variants were not significantly associated with reproductive hormones or semen quality parameters. Conclusion: This study provides evidence that carriers of FLG loss-of-function alleles may have higher internal exposure to phthalates, possibly due to increased transepidermal absorption. FLG loss-of-function variants may indicate susceptible populations for which special attention to transepidermal absorption of chemicals and medication may be warranted. 

Public Health And Safety; Dermatitis; Studies; Cosmetics industry; Allergies; Skin care products