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Iron Metabolism Genes, Low-Level Lead Exposure, and QT Interval

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 meta...

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Autores principales: Park, Sung Kyun, Hu, Howard, Wright, Robert O., Schwartz, Joel, Cheng, Yawen, Sparrow, David, Vokonas, Pantel S., Weisskopf, Marc G.
Formato: Texto
Lenguaje:English
Publicado: National Institute of Environmental Health Sciences 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2627870/
https://www.ncbi.nlm.nih.gov/pubmed/19165391
http://dx.doi.org/10.1289/ehp.11559
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author Park, Sung Kyun
Hu, Howard
Wright, Robert O.
Schwartz, Joel
Cheng, Yawen
Sparrow, David
Vokonas, Pantel S.
Weisskopf, Marc G.
author_facet Park, Sung Kyun
Hu, Howard
Wright, Robert O.
Schwartz, Joel
Cheng, Yawen
Sparrow, David
Vokonas, Pantel S.
Weisskopf, Marc G.
author_sort Park, Sung Kyun
collection PubMed
description 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.
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spelling pubmed-26278702009-01-22 Iron Metabolism Genes, Low-Level Lead Exposure, and QT Interval Park, Sung Kyun Hu, Howard Wright, Robert O. Schwartz, Joel Cheng, Yawen Sparrow, David Vokonas, Pantel S. Weisskopf, Marc G. Environ Health Perspect Research 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. National Institute of Environmental Health Sciences 2009-01 2008-08-22 /pmc/articles/PMC2627870/ /pubmed/19165391 http://dx.doi.org/10.1289/ehp.11559 Text en http://creativecommons.org/publicdomain/mark/1.0/ Publication of EHP lies in the public domain and is therefore without copyright. All text from EHP may be reprinted freely. Use of materials published in EHP should be acknowledged (for example, ?Reproduced with permission from Environmental Health Perspectives?); pertinent reference information should be provided for the article from which the material was reproduced. Articles from EHP, especially the News section, may contain photographs or illustrations copyrighted by other commercial organizations or individuals that may not be used without obtaining prior approval from the holder of the copyright.
spellingShingle Research
Park, Sung Kyun
Hu, Howard
Wright, Robert O.
Schwartz, Joel
Cheng, Yawen
Sparrow, David
Vokonas, Pantel S.
Weisskopf, Marc G.
Iron Metabolism Genes, Low-Level Lead Exposure, and QT Interval
title Iron Metabolism Genes, Low-Level Lead Exposure, and QT Interval
title_full Iron Metabolism Genes, Low-Level Lead Exposure, and QT Interval
title_fullStr Iron Metabolism Genes, Low-Level Lead Exposure, and QT Interval
title_full_unstemmed Iron Metabolism Genes, Low-Level Lead Exposure, and QT Interval
title_short Iron Metabolism Genes, Low-Level Lead Exposure, and QT Interval
title_sort iron metabolism genes, low-level lead exposure, and qt interval
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2627870/
https://www.ncbi.nlm.nih.gov/pubmed/19165391
http://dx.doi.org/10.1289/ehp.11559
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