title: Iron metabolism genes, low-level lead exposure, and QT interval.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan 48109, USA. sungkyun@umich.edu
authors.forename: Sung Kyun
authors.initials: SK
authors.lastname: Park
authors.forename: Howard
authors.initials: H
authors.lastname: Hu
authors.forename: Robert O
authors.initials: RO
authors.lastname: Wright
authors.forename: Joel
authors.initials: J
authors.lastname: Schwartz
authors.forename: Yawen
authors.initials: Y
authors.lastname: Cheng
authors.forename: David
authors.initials: D
authors.lastname: Sparrow
authors.forename: Pantel S
authors.initials: PS
authors.lastname: Vokonas
authors.forename: Marc G
authors.initials: MG
authors.lastname: Weisskopf
mesh_terms: D001483:Base Sequence; D017931:DNA Primers; D004562:Electrocardiography; D004781:Environmental Exposure; D007501:Iron / Q000378:metabolism*; D007854:Lead / Q000633:toxicity*
chemical_list: D017931:DNA Primers; D007854:Lead; D007501:Iron