Published Online
on December 4, 2006

A more recent version of this article appeared on December 19, 2006

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Submitted on June 5, 2006
Revised on September 14, 2006
Accepted on October 10, 2006

HFE Genotype, Particulate Air Pollution, and Heart Rate Variability. A Gene-Environment Interaction

Sung Kyun Park ScD^*, Marie S. O’Neill PhD, Robert O. Wright MD, MPH, Howard Hu MD, ScD, Pantel S. Vokonas MD, David Sparrow DSc, Helen Suh ScD, and Joel Schwartz PhD

From Department of Environmental Health (S.K.P., R.O.W., H.H., H.S., J.S.), Harvard School of Public Health, Boston, Mass; Department of Epidemiology (M.S.O.), University of Michigan School of Public Health, Ann Arbor, Mich; Channing Laboratory (R.O.W., H.H., D.S., J.S.), Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass; VA Normative Aging Study (P.S.V., D.S.), Veterans Affairs Boston Healthcare System and the Department of Medicine, Boston University School of Medicine, Boston, Mass.

^* To whom correspondence should be addressed. E-mail: sungkyun{at}umich.edu.

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.

Methods and Results--We investigated the association between particulate matter 2.5 µm 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 2.5 µm in aerodynamic diameter in relation to heart rate variability, controlling for potential confounders. A 10-µg/m³ increase in particulate matter 2.5 µm 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 2.5 µm 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.

Key words: air pollution • genes • epidemiology • nervous system, autonomic • metals

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