Associations of Filaggrin Gene Loss-of-Function Variants with Urinary Phthalate Metabolites and Testicular Function in Young Danish Men
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Citation: 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. Associations of Filaggrin Gene Loss-of-Function Variants with Urinary Phthalate Metabolites and Testicular Function in Young Danish Men. Environ Health Perspect; http://dx.doi.org/10.1289/ehp.1306720.
Received: 27 February 2013
Accepted: 23 December 2013
Advance Publication: 3 January 2014
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 null allele carriers 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. Urinary concentrations of 14 phthalate metabolites were measured, as well as serum levels of reproductive hormones and 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 (95% CI: 16, 51%). FLG null variants were not significantly associated with reproductive hormones or semen quality parameters.
Conclusion: This study provides evidence that FLG loss-of-function allele carriers may have higher internal exposure to phthalates, possibly due to increased trans-epidermal absorption. FLG loss-of-function variants may indicate susceptible populations in which special attention to trans-epidermal absorption of chemicals and medication may be warranted.
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