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dc.contributor.authorHumblet, Olivier
dc.contributor.authorKorrick, Susan A.
dc.contributor.authorWilliams, Paige L.
dc.contributor.authorSergeyev, Oleg
dc.contributor.authorEmond, Claude
dc.contributor.authorBirnbaum, Linda S.
dc.contributor.authorBurns, Jane S.
dc.contributor.authorAltshul, Larisa
dc.contributor.authorPatterson, Donald G. Jr.
dc.contributor.authorTurner, Wayman E.
dc.contributor.authorLee, Mary M.
dc.contributor.authorRevich, Boris
dc.contributor.authorHauser, Russ
dc.date2022-08-11T08:08:03.000
dc.date.accessioned2022-08-23T15:40:35Z
dc.date.available2022-08-23T15:40:35Z
dc.date.issued2013-01-01
dc.date.submitted2013-03-22
dc.identifier.citationEnviron Health Perspect. 2013 Jan;121(1):111-7. doi: 10.1289/ehp.1205278. <a href="http://dx.doi.org/10.1289/ehp.1205278">Link to article on publisher's site</a>
dc.identifier.issn0091-6765 (Linking)
dc.identifier.doi10.1289/ehp.1205278
dc.identifier.pmid23060366
dc.identifier.urihttp://hdl.handle.net/20.500.14038/26436
dc.description.abstractBACKGROUND: 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.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=23060366&dopt=Abstract">Link to Article in PubMed</a>
dc.rights<p>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.</p>
dc.subjectHydrocarbons, Chlorinated
dc.subjectPesticides
dc.subjectHexachlorobenzene
dc.subjectGrowth and Development
dc.subjectRussia
dc.subjectEndocrinology, Diabetes, and Metabolism
dc.subjectEnvironmental Public Health
dc.subjectMedical Toxicology
dc.subjectPediatrics
dc.titleGenetic modification of the association between peripubertal dioxin exposure and pubertal onset in a cohort of Russian boys
dc.typeJournal Article
dc.source.journaltitleEnvironmental health perspectives
dc.source.volume121
dc.source.issue1
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1117&amp;context=cellbiology_pp&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/cellbiology_pp/118
dc.identifier.contextkey3943379
refterms.dateFOA2022-08-23T15:40:36Z
html.description.abstract<p>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.</p> <p>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.</p> <p>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.</p> <p>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.</p> <p>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.</p>
dc.identifier.submissionpathcellbiology_pp/118
dc.contributor.departmentDepartment of Cell and Developmental Biology
dc.contributor.departmentDepartment of Pediatrics
dc.source.pages111-7


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