dc.contributor.author | Park, Sung Kyun | |
dc.contributor.author | Hu, Howard | |
dc.contributor.author | Wright, Robert O. | |
dc.contributor.author | Schwartz, Joel David | |
dc.contributor.author | Cheng, Yawen | |
dc.contributor.author | Sparrow, David | |
dc.contributor.author | Vokonas, Pantel S | |
dc.contributor.author | Weisskopf, Marc G. | |
dc.date.accessioned | 2011-05-15T19:41:29Z | |
dc.date.issued | 2008 | |
dc.identifier.citation | Park, Sung Kyun, Howard Hu, Robert O. Wright, Joel Schwartz, Yawen Cheng, David Sparrow, Pantel S. Vokonas, and Marc G. Weisskopf. 2009. Iron metabolism genes, low-level lead exposure, and QT interval. Environmental Health Perspectives 117(1): 80-85. | en_US |
dc.identifier.issn | 0091-6765 | en_US |
dc.identifier.uri | http://nrs.harvard.edu/urn-3:HUL.InstRepos:4889495 | |
dc.description.abstract | Background: Cumulative exposure to lead has been shown to be associated with depression of electrocardiographic conduction, such as QT interval (time from start of the Q wave to end of the T wave). Because iron can enhance the oxidative effects of lead, we examined whether polymorphisms in iron metabolism genes [hemochromatosis (\(HFE\)), transferrin (\(TF\)) C2, and heme oxygenase-1 (\(HMOX-1\))] increase susceptibility to the effects of lead on QT interval in 613 community-dwelling older men. Methods: We used standard 12-lead electrocardiograms, K-shell X-ray fluorescence, and graphite furnace atomic absorption spectrometry to measure QT interval, bone lead, and blood lead levels, respectively. Results: A one-interquartile-range increase in tibia lead level (13 μg/g) was associated with a 11.35-msec [95% confidence interval (CI), 4.05–18.65 msec] and a 6.81-msec (95% CI, 1.67–11.95 msec) increase in the heart-rate–corrected QT interval among persons carrying long \(HMOX-1\) alleles and at least one copy of an \(HFE\) variant, respectively, but had no effect in persons with short and middle \(HMOX-1\) alleles and the wild-type HFE genotype. The lengthening of the heart-rate–corrected QT interval with higher tibia lead and blood lead became more pronounced as the total number (0 vs. 1 vs. ≥2) of gene variants increased (tibia, \(p\)-trend = 0.01; blood, \(p\)-trend = 0.04). This synergy seems to be driven by a joint effect between \(HFE\) variant and \(HMOX-1\) L alleles. Conclusion: We found evidence that gene variants related to iron metabolism increase the impacts of low-level lead exposure on the prolonged QT interval. This is the first such report, so these results should be interpreted cautiously and need to be independently verified. | 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.11559 | en_US |
dc.relation.hasversion | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2627870/pdf/ | en_US |
dash.license | LAA | |
dc.subject | gene–environment interaction | en_US |
dc.subject | heme oxygenase-1 | en_US |
dc.subject | hemochromatosis | en_US |
dc.subject | iron | en_US |
dc.subject | lead | en_US |
dc.subject | transferrin | en_US |
dc.title | Iron Metabolism Genes, Low-Level Lead Exposure, and QT Interval | 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 | Schwartz, Joel David | |
dc.date.available | 2011-05-15T19:41:29Z | |
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 |
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 | SPH^Environmental+Occupational Medicine+Epi | en_US |
dash.affiliation.other | SPH^Student Stipends | en_US |
dc.identifier.doi | 10.1289/ehp.11559 | * |
dash.contributor.affiliated | Weisskopf, Marc | |
dash.contributor.affiliated | Vokonas, Pantel | |
dash.contributor.affiliated | Wright, Robert | |
dash.contributor.affiliated | Sparrow, David | |
dash.contributor.affiliated | Schwartz, Joel | |
dc.identifier.orcid | 0000-0002-2557-150X | |