Associations of Filaggrin Gene Loss-of-Function Variants with Urinary Phthalate Metabolites and Testicular Function in Young Danish Men

TY - JOUR

T1 - Associations of Filaggrin Gene Loss-of-Function Variants with Urinary Phthalate Metabolites and Testicular Function in Young Danish Men

AU - Joensen, Ulla Nordström

AU - Jørgensen, Niels

AU - Meldgaard, Michael

AU - Frederiksen, Hanne

AU - Andersson, Anna-Maria

AU - Menné, Torkil

AU - Johansen, Jeanne Duus

AU - Carlsen, Berit Christina

AU - Stender, Steen

AU - Szecsi, Pal Bela

AU - Skakkebæk, Niels Erik

AU - De Meyts, Ewa Rajpert

AU - Thyssen, Jacob P

PY - 2014/4

Y1 - 2014/4

N2 - 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.

AB - 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.

KW - Adolescent

KW - Adult

KW - Cross-Sectional Studies

KW - Genetic Predisposition to Disease

KW - Genotype

KW - Humans

KW - Intermediate Filament Proteins

KW - Male

KW - Phthalic Acids

KW - Testis

KW - Young Adult

U2 - 10.1289/ehp.1306720

DO - 10.1289/ehp.1306720

M3 - Journal article

C2 - 24380925

SN - 0091-6765

VL - 122

SP - 345

EP - 350

JO - Environmental Health Perspectives

JF - Environmental Health Perspectives

IS - 4

ER -