This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 114/25/2798    most recent CIRCULATIONAHA.106.643197v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Park, S. K. Articles by Schwartz, J. Search for Related Content PubMed PubMed Citation Articles by Park, S. K. Articles by Schwartz, J. Related Collections Electrophysiology Epidemiology Autonomic, reflex, and neurohumoral control of circulation Oxidant stress

(Circulation. 2006;114:2798-2805.)
© 2006 American Heart Association, Inc.

Genetics

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; 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.

Correspondence to Sung Kyun Park, ScD, Department of Environmental Health Sciences, University of Michigan School of Public Health, 109 S Observatory St, SPH II-M6240, Ann Arbor, MI 48109. E-mail sungkyun{at}umich.edu

Received June 5, 2006; revision received September 14, 2006; accepted October 10, 2006.

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.

---

 

CLINICAL PERSPECTIVE

This article has been cited by other articles:

				C Ren, A Baccarelli, E Wilker, H Suh, D Sparrow, P Vokonas, R Wright, and J Schwartz Lipid and endothelium-related genes, ambient particulate matter, and heart rate variability--the VA Normative Aging Study J Epidemiol Community Health, January 1, 2010; 64(01): 49 - 56. [Abstract] [Full Text] [PDF]

				A. Baccarelli Breathe Deeply into Your Genes!: Genetic Variants and Air Pollution Effects Am. J. Respir. Crit. Care Med., March 15, 2009; 179(6): 431 - 432. [Full Text] [PDF]

				A. Peters, S. Greven, I. M. Heid, F. Baldari, S. Breitner, T. Bellander, C. Chrysohoou, T. Illig, B. Jacquemin, W. Koenig, et al. Fibrinogen Genes Modify the Fibrinogen Response to Ambient Particulate Matter Am. J. Respir. Crit. Care Med., March 15, 2009; 179(6): 484 - 491. [Abstract] [Full Text] [PDF]

				A. Baccarelli, P. A. Cassano, A. Litonjua, S. K. Park, H. Suh, D. Sparrow, P. Vokonas, and J. Schwartz Cardiac Autonomic Dysfunction: Effects From Particulate Air Pollution and Protection by Dietary Methyl Nutrients and Metabolic Polymorphisms Circulation, April 8, 2008; 117(14): 1802 - 1809. [Abstract] [Full Text] [PDF]

				F. B. Hu The Iron-Heart Hypothesis: Search for the Ironclad Evidence JAMA, February 14, 2007; 297(6): 639 - 641. [Full Text] [PDF]