Hereditary Hemochromatosis and Risk of Ischemic Heart Disease

Author:

Ellervik Christina1,Tybjærg-Hansen Anne1,Grande Peer1,Appleyard Merete1,Nordestgaard Børge G.1

Affiliation:

1. From the Department of Clinical Biochemistry, Herlev University Hospital (C.E., B.G.N.), Department of Clinical Biochemistry (A.T.-H.), and Department of Cardiology (P.G.), Rigshospitalet, Copenhagen University Hospital, and The Copenhagen City Heart Study, Bispebjerg University Hospital (A.T.-H., M.A., B.G.N.), University of Copenhagen, Copenhagen, Denmark.

Abstract

Background— We tested the hypothesis that the hereditary hemochromatosis genotypes C282Y/C282Y, C282Y/H63D, or C282Y/wild-type are risk factors for ischemic heart disease (IHD) and myocardial infarction (MI). Methods and Results— We performed a prospective study of 9178 individuals from the Danish general population followed up for 24 years, during which 1035 and 511 developed IHD and MI, respectively, and a case-control study of 2441 and 1113 IHD and MI cases versus 8080 controls. C282Y/C282Y, C282Y/H63D, and C282Y/wild-type versus wild-type/wild-type individuals were not associated with increased risk of IHD or MI in prospective studies, overall or stratified by gender. We had 90% power to detect a hazard ratio for IHD of 3.4 for C282Y/C282Y, 1.9 for C282Y/H63D, and 1.3 for C282Y/wild-type versus wild-type/wild-type. Furthermore, these genotypes were not associated with increased risk of IHD or MI in case-control studies, overall or stratified by gender. We had 90% power to detect an odds ratio for IHD of 3.6 for C282Y/C282Y, 1.8 for C282Y/H63D, and 1.3 for C282Y/wild-type versus wild-type/wild-type. Conclusions— In these studies, hereditary hemochromatosis C282Y/C282Y, C282Y/H63D, and C282Y/wild-type genotypes were not associated with IHD or MI; however, the study lacked the power to exclude the possibility that C282Y/C282Y and C282Y/H63D individuals have a modestly increased risk of IHD or MI.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Physiology (medical),Cardiology and Cardiovascular Medicine

Reference27 articles.

1. Hereditary haemochromatosis and the hypothesis that iron depletion protects against ischemic heart disease

2. Beutler E Bothwell TH Charlton RW Motulsky AG. Hereditary hemochromatosis. In: Scriver CR Beaudet AL Sly WS Valle D eds. The Metabolic and Molecular Bases of Inherited Disease. New York NY: McGraw-Hill; 2001: 3127–3162.

3. Iron, Atherosclerosis, and Ischemic Heart Disease

4. C282Y mutation in the HLA-H Gene is Not a Risk Factor for Patients with Myocardial Infarction

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