HFE genotype, particulate air pollution, and heart rate variability: a gene-environment interaction.
BACKGROUND
Particulate air pollution has been associated with cardiovascular mortality and morbidity. Transition metals such as iron bound to the particles may be responsible for those associations. The protein product of the hemochromatosis (HFE) gene modulates uptake of iron and divalent cations from pulmonary sources and reduces their toxicity. Two HFE polymorphisms (C282Y and H63D) associated with increased iron uptake may modify the effect of metal-rich particles on the cardiovascular system.


RESULTS
We investigated the association between particulate matter < or = 2.5 microm in aerodynamic diameter and heart rate variability in 518 older men from the Normative Aging Study who were examined between November 2000 and December 2004. Linear regression models were fit to evaluate interactions between HFE genotype and particulate matter < or = 2.5 microm in aerodynamic diameter in relation to heart rate variability, controlling for potential confounders. A 10-microg/m3 increase in particulate matter < or = 2.5 microm in aerodynamic diameter during the 48 hours before heart rate variability measurement was associated with a 31.7% (95% CI, 10.3% to 48.1%) decrease in the high-frequency component of heart rate variability in persons with the wild-type genotype, whereas no relationship in the high-frequency component was observed in persons with either HFE variant. The difference in effect of particulate matter < or = 2.5 microm in aerodynamic diameter on the high-frequency component between persons with and without HFE variants was significant (P for interaction=0.02).


CONCLUSIONS
The effect of particles on cardiac autonomic function was shielded in subjects with at least 1 copy of an HFE variant compared with wild-type subjects. Transition metals, including iron, bound to ambient particles and the related oxidative stress may play an important role in cardiac toxicity of particles.
Park
Sung Kyun
SK
Department of Environmental Health, Harvard School of Public Health, Boston, Mass, USA. sungkyun@umich.edu
O'Neill
Marie S
MS
Wright
Robert O
RO
Hu
Howard
H
Vokonas
Pantel S
PS
Sparrow
David
D
Suh
Helen
H
Schwartz
Joel
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000397:Air Pollution; D019943:Amino Acid Substitution; D001900:Boston; D015331:Cohort Studies; D014644:Genetic Variation; D005838:Genotype; D006339:Heart Rate / Q000502:physiology*; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D052638:Particulate Matter; D011110:Polymorphism, Genetic; D012044:Regression Analysis; D014887:Weather
C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D052638:Particulate Matter; D007501:Iron