Associations of Filaggrin Gene Loss-of-Function Variants with Urinary Phthalate Metabolites and Testicular Function in Young Danish Men
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Associations of Filaggrin Gene Loss-of-Function Variants with Urinary Phthalate Metabolites and Testicular Function in Young Danish Men. / Joensen, Ulla Nordström; Jørgensen, Niels; Meldgaard, Michael; Frederiksen, Hanne; Andersson, Anna-Maria; Menné, Torkil; Johansen, Jeanne Duus; Carlsen, Berit Christina; Stender, Steen; Szecsi, Pal Bela; Skakkebæk, Niels Erik; De Meyts, Ewa Rajpert; Thyssen, Jacob P.
In: Environmental Health Perspectives, Vol. 122, No. 4, 04.2014, p. 345-350.Research output: Contribution to journal › Journal article › Research › peer-review
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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
VL - 122
SP - 345
EP - 350
JO - Environmental Health Perspectives
JF - Environmental Health Perspectives
SN - 0091-6765
IS - 4
ER -
ID: 138224851