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dc.contributor.authorHopkins, Marianne
dc.contributor.authorEttinger, Adrienne S
dc.contributor.authorHernández-Avila, Mauricio
dc.contributor.authorSchwartz, Joel David
dc.contributor.authorTéllez-Rojo, Martha María
dc.contributor.authorLamadrid-Figueroa, Héctor
dc.contributor.authorBellinger, David C.
dc.contributor.authorHu, Howard
dc.contributor.authorWright, Robert O.
dc.date.accessioned2011-04-29T04:41:43Z
dc.date.issued2008
dc.identifier.citationHopkins, Marianne R., Adrienne S. Ettinger, Mauricio Hernández-Avila, Joel Schwartz, Martha Marí­a Téllez-Rojo, Héctor Lamadrid-Figueroa, David Bellinger, Howard Hu, and Robert O. Wright. 2008. Variants in iron metabolism genes predict higher blood lead levels in young children. Environmental Health Perspectives 116(9): 1261-1266.en_US
dc.identifier.issn0091-6765en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:4879210
dc.description.abstractBackground: Given the association between iron deficiency and lead absorption, we hypothesized that variants in iron metabolism genes would predict higher blood lead levels in young children. Objective: We examined the association between common missense variants in the hemochromatosis (HFE) and transferrin (TF) genes and blood lead levels in 422 Mexican children. Methods: Archived umbilical cord blood samples were genotyped for HFE (H63D and C282Y) and TF (P570S) variants. Blood lead was measured at 24, 30, 36, 42, and 48 months of age. A total of 341 subjects had at least one follow-up blood lead level available and data available on covariates of interest for inclusion in the longitudinal analyses. We used random-effects models to examine the associations between genotype (HFE, TF, and combined HFE + TF) and repeated measures of blood lead, adjusting for maternal blood lead at delivery and child’s concurrent anemia status. Results: Of 422 children genotyped, 17.7, 3.3, and 18.9% carried the HFE H63D, HFE C282Y, and TF P570S variants, respectively. One percent of children carried both the HFE C282Y and TF P570S variants, and 3% of children carried both the HFE H63D and TF P570S variants. On average, carriers of either the HFE (β = 0.11, p = 0.04) or TF (β = 0.10, p = 0.08) variant had blood lead levels that were 11% and 10% higher, respectively, than wild-type subjects. In models examining the dose effect, subjects carrying both variants (β = 0.41, p = 0.006) had blood lead 50% higher than wild-type subjects and a significantly higher odds of having a blood lead level > 10 μg/dL (odds ratio = 18.3; 95% confidence interval, 1.9–177.1). Conclusions: Iron metabolism gene variants modify lead metabolism such that HFE variants are associated with increased blood lead levels in young children. The joint presence of variant alleles in the HFE and TF genes showed the greatest effect, suggesting a gene-by-gene-by-environment interaction.en_US
dc.language.isoen_USen_US
dc.publisherNational Institute of Environmental Health Sciencesen_US
dc.relation.isversionofdoi:10.1289/ehp.11233en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2535632/pdf/en_US
dash.licenseLAA
dc.subjectC282Yen_US
dc.subjectchildrenen_US
dc.subjectH63Den_US
dc.subjecthemochromatosisen_US
dc.subjectironen_US
dc.subjectleaden_US
dc.subjectP570Sen_US
dc.subjectpolymorphismen_US
dc.subjecttransferrinen_US
dc.subjectchildren's healthen_US
dc.titleVariants in iron metabolism genes predict higher blood lead levels in young childrenen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalEnvironmental Health Perspectivesen_US
dash.depositing.authorHopkins, Marianne
dc.date.available2011-04-29T04:41:43Z
dash.affiliation.otherHMS^Medicine-Brigham and Women's Hospitalen_US
dash.affiliation.otherSPH^Exposure Epidemiology and Risk Programen_US
dash.affiliation.otherHMS^Medicine-Brigham and Women's Hospitalen_US
dash.affiliation.otherSPH^Exposure Epidemiology and Risk Programen_US
dash.affiliation.otherHMS^Neurology-Children's Hospitalen_US
dash.affiliation.otherSPH^Exposure Epidemiology and Risk Programen_US
dash.affiliation.otherHMS^Medicine-Brigham and Women's Hospitalen_US
dash.affiliation.otherSPH^Environmental+Occupational Medicine+Epien_US
dash.affiliation.otherHMS^Pediatrics-Children's Hospitalen_US
dc.identifier.doi10.1289/ehp.11233*
dash.contributor.affiliatedHopkins, Marianne
dash.contributor.affiliatedEttinger, Adrienne
dash.contributor.affiliatedBellinger, David
dash.contributor.affiliatedWright, Robert
dash.contributor.affiliatedSchwartz, Joel


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