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Relation of HFE gene mutations, high iron stores and early onset coronary artery disease
B A Nassar1, E M Zayed, L M Title
1Department of Pathology, Dalhousie University Faculty of Medicine, Halifax, Nova Scotia. nassar@is.dal.ca
Insights
HFE gene mutations (C282Y, H63D) do not appear to be a major risk factor for early-onset coronary artery disease (CAD). Higher iron stores were observed in males with early-onset CAD, but this was unrelated to HFE mutations.
Area of Science:
- Cardiovascular Medicine
- Genetics
- Iron Metabolism
Background:
- Elevated iron stores are linked to increased risk of acute myocardial infarction.
- HFE gene mutations (C282Y, H63D) are associated with hereditary hemochromatosis and high iron stores.
- The role of HFE mutations in coronary artery disease (CAD) predisposition was previously uninvestigated.
Purpose of the Study:
- To investigate the impact of HFE gene mutations on the risk of developing coronary artery disease (CAD).
- To determine if HFE mutations contribute to early-onset CAD in patients without hereditary hemochromatosis.
Main Methods:
- Study included 300 patients with CAD, divided into early-onset (under 50) and late-onset groups.
- Molecular analysis was performed to assess the prevalence of C282Y and H63D HFE mutations.
- Plasma ferritin levels were measured to evaluate iron stores.
Main Results:
- No significant difference in HFE mutation prevalence was found between early-onset and late-onset CAD groups.
- Males with early-onset CAD exhibited higher plasma ferritin levels compared to late-onset males, irrespective of HFE mutation status.
- Plasma ferritin levels did not differ significantly between female groups.
Conclusions:
- Higher iron stores are associated with early-onset CAD in males, but this association is not linked to HFE gene mutations (C282Y, H63D).
- HFE mutations are unlikely to be a significant risk factor for high iron stores contributing to early-onset CAD.
- The major histocompatibility complex (MHC) locus's association with delayed-onset CAD appears unrelated to HFE in this patient cohort.
Objective:
To determine the impact of mutations in the HFE gene (human leukocyte antigen H) on predisposition to coronary artery disease (CAD) in patients not diagnosed with hereditary hemochromatosis.
Background:
Elevated iron stores can predispose to acute myocardial infarction. Two mutations (C282Y and H63D) in the novel major histocompatibility complex (MHC) class 1 gene HFE were found in most patients with hereditary hemochromatosis causing high iron stores. The effect of these mutations on predisposition to CAD has not been investigated previously.
Methods:
Three hundred patients with a history of myocardial infarction or angina pectoris and angiographically documented CAD were studied. Patients were divided into two groups: group 1 (150 patients), manifesting early onset CAD and presenting with these findings under age 50 years; and group 2 (150 patients), presenting for the first time over age 65 years. Prevalence of the C282Y and H63D mutations was assessed by molecular analysis, and plasma ferritin was measured immunochemically.
Results:
There was no difference in the prevalence of homozygous, heterozygous or compound heterozygous (C282Y/H63D) states between the groups. Males in group 1 had higher plasma ferritin than those in group 2 (234 +/- 174 micrograms/L versus 136 +/- 103 micrograms/L, P < 0.0001), but this was not significantly different in females (75 +/- 54 micrograms/L versus 92 +/- 73 micrograms/L, P = 0.26). Ferritin remained higher in group 1 than in group 2 males after exclusion of mutation carriers (195 +/- 121 micrograms/L versus 109 +/- 76 micrograms/L, respectively, P < 0.0001), but did not change in females.
Conclusions:
Higher iron stores were found in males with early onset CAD. This association was not related to the C282Y or H63D mutation in HFE. It is suggested that association of the MHC locus with delayed onset CAD is probably unrelated to HFE in these patients, and that HFE mutations are not a major risk factor in the development of high iron stores in early onset CAD.