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Environ Health Perspect. 2009 Jan;117(1):80-5. doi: 10.1289/ehp.11559. Epub 2008 Aug 22.

Iron metabolism genes, low-level lead exposure, and QT interval.

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  • 1Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan 48109, USA.



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.


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.


A one-interquartile-range increase in tibia lead level (13 mug/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.


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.


gene–environment interaction; heme oxygenase-1; hemochromatosis; iron; lead; transferrin

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