Hereditary hemochromatosis and risk of ischemic heart disease: a prospective study and a case-control study.

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.