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

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

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Title: Iron Metabolism Genes, Low-Level Lead Exposure, and QT Interval
Author: Hu, Howard; Cheng, Yawen; Park, Sung Kyun; Wright, Robert O.; Schwartz, Joel David; Sparrow, David; Vokonas, Pantel S; Weisskopf, Marc G.

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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.
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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.
Published Version: doi:10.1289/ehp.11559
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