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

Authors: Park, Sung Kyun; Hu, Howard; Wright, Robert O; Schwartz, Joel; Cheng, Yawen; Sparrow, David; Vokonas, Pantel S; Weisskopf, Marc G

Published In Environ Health Perspect, (2009 Jan)

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 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. 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.

PubMed ID: 19165391 Exiting the NIEHS site

MeSH Terms: No MeSH terms associated with this publication

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