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Article
Genetic modification of the association between peripubertal dioxin exposure and pubertal onset in a cohort of Russian boys
Cell and Developmental Biology Publications and Presentations
  • Olivier Humblet, Harvard School of Public Health
  • Susan A. Korrick, Harvard Medical School
  • Paige L. Williams, Harvard School of Public Health
  • Oleg Sergeyev, Samara State Medical University
  • Claude Emond, University of Montreal
  • Linda S. Birnbaum, National Institutes of Health
  • Jane S. Burns, Harvard University
  • Larisa Altshul, Environmental Health and Engineering, Inc.
  • Donald G. Patterson, Jr., EnviroSolutions Consulting, Inc.
  • Wayman E. Turner, Centers for Disease Control and Prevention
  • Mary M. Lee, University of Massachusetts Medical School
  • Boris Revich, Russian Academy of Sciences
  • Russ Hauser, Harvard School of Public Health
UMMS Affiliation
Department of Pediatrics; Department of Cell and Developmental Biology
Date
1-1-2013
Document Type
Article
Subjects
Hydrocarbons, Chlorinated; Pesticides; Hexachlorobenzene; Growth and Development; Russia
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.
Rights and Permissions
Citation: Environ Health Perspect. 2013 Jan;121(1):111-7. doi: 10.1289/ehp.1205278. Link to article on publisher's site
Comments

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.

Related Resources
Link to Article in PubMed
PubMed ID
23060366
Citation Information
Olivier Humblet, Susan A. Korrick, Paige L. Williams, Oleg Sergeyev, et al.. "Genetic modification of the association between peripubertal dioxin exposure and pubertal onset in a cohort of Russian boys" Vol. 121 Iss. 1 (2013) ISSN: 0091-6765 (Linking)
Available at: http://works.bepress.com/mary_lee/12/