Variants in iron metabolism genes predict higher blood lead levels in young children

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Variants in iron metabolism genes predict higher blood lead levels in young children

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dc.contributor.author Hernández-Avila, Mauricio
dc.contributor.author Téllez-Rojo, Martha María
dc.contributor.author Lamadrid-Figueroa, Héctor
dc.contributor.author Hu, Howard
dc.contributor.author Hopkins, Marianne
dc.contributor.author Ettinger, Adrienne S
dc.contributor.author Schwartz, Joel David
dc.contributor.author Bellinger, David C.
dc.contributor.author Wright, Robert O.
dc.date.accessioned 2011-04-29T04:41:43Z
dc.date.issued 2008
dc.identifier.citation Hopkins, 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.issn 0091-6765 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:4879210
dc.description.abstract Background: 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.iso en_US en_US
dc.publisher National Institute of Environmental Health Sciences en_US
dc.relation.isversionof doi:10.1289/ehp.11233 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2535632/pdf/ en_US
dash.license LAA
dc.subject C282Y en_US
dc.subject children en_US
dc.subject H63D en_US
dc.subject hemochromatosis en_US
dc.subject iron en_US
dc.subject lead en_US
dc.subject P570S en_US
dc.subject polymorphism en_US
dc.subject transferrin en_US
dc.subject children's health en_US
dc.title Variants in iron metabolism genes predict higher blood lead levels in young children en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal Environmental Health Perspectives en_US
dash.depositing.author Hopkins, Marianne
dc.date.available 2011-04-29T04:41:43Z
dash.affiliation.other HMS^Medicine-Brigham and Women's Hospital en_US
dash.affiliation.other SPH^Exposure Epidemiology and Risk Program en_US
dash.affiliation.other HMS^Medicine-Brigham and Women's Hospital en_US
dash.affiliation.other SPH^Exposure Epidemiology and Risk Program en_US
dash.affiliation.other HMS^Neurology-Children's Hospital en_US
dash.affiliation.other SPH^Exposure Epidemiology and Risk Program en_US
dash.affiliation.other HMS^Medicine-Brigham and Women's Hospital en_US
dash.affiliation.other SPH^Environmental+Occupational Medicine+Epi en_US
dash.affiliation.other HMS^Pediatrics-Children's Hospital en_US

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