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    Genetic modification of the association between peripubertal dioxin exposure and pubertal onset in a cohort of Russian boys

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    Authors
    Humblet, Olivier
    Korrick, Susan A.
    Williams, Paige L.
    Sergeyev, Oleg
    Emond, Claude
    Birnbaum, Linda S.
    Burns, Jane S.
    Altshul, Larisa
    Patterson, Donald G. Jr.
    Turner, Wayman E.
    Lee, Mary M.
    Revich, Boris
    Hauser, Russ
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    UMass Chan Affiliations
    Department of Cell and Developmental Biology
    Department of Pediatrics
    Document Type
    Journal Article
    Publication Date
    2013-01-01
    Keywords
    Hydrocarbons, Chlorinated
    Pesticides
    Hexachlorobenzene
    Growth and Development
    Russia
    Endocrinology, Diabetes, and Metabolism
    Environmental Public Health
    Medical Toxicology
    Pediatrics
    
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    Abstract
    BACKGROUND: Exposure to dioxins has been associated with delayed pubertal onset in both epidemiologic and animal studies. Whether genetic polymorphisms may modify this association is currently unknown. Identifying such genes could provide insight into mechanistic pathways. This is one of the first studies to assess genetic susceptibility to dioxins. OBJECTIVES: We evaluated whether common polymorphisms in genes affecting either molecular responses to dioxin exposure or pubertal onset influence the association between peripubertal serum dioxin concentration and male pubertal onset. METHODS: In this prospective cohort of Russian adolescent boys (n = 392), we assessed gene-environment interactions for 337 tagging single-nucleotide polymorphisms (SNPs) from 46 candidate genes and two intergenic regions. Dioxins were measured in the boys' serum at age 8-9 years. Pubertal onset was based on testicular volume and on genitalia staging. Statistical approaches for controlling for multiple testing were used, both with and without prescreening for marginal genetic associations. RESULTS: After accounting for multiple testing, two tag SNPs in the glucocorticoid receptor (GR/NR3C1) gene and one in the estrogen receptor-alpha (ESR1) gene were significant (q < 0.2) modifiers of the association between peripubertal serum dioxin concentration and male pubertal onset defined by genitalia staging, although not by testicular volume. The results were sensitive to whether multiple comparison adjustment was applied to all gene-environment tests or only to those with marginal genetic associations. CONCLUSIONS: Common genetic polymorphisms in the glucocorticoid receptor and estrogen receptor-alpha genes may modify the association between peripubertal serum dioxin concentration and pubertal onset. Further studies are warranted to confirm these findings.
    Source
    Environ Health Perspect. 2013 Jan;121(1):111-7. doi: 10.1289/ehp.1205278. Link to article on publisher's site
    DOI
    10.1289/ehp.1205278
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/26436
    PubMed ID
    23060366
    Related Resources
    Link to Article in PubMed
    Rights

    Environmental Health Perspectives is a publication of the U.S. government. Publication of Environmental Health Perspectives lies in the public domain and is therefore without copyright.

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    10.1289/ehp.1205278
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