title: Relation of HFE gene mutations, high iron stores and early onset coronary artery disease.
abstract: 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.
authors.affiliation: Department of Pathology, Dalhousie University Faculty of Medicine, Halifax, Nova Scotia. nassar@is.dal.ca
authors.forename: B A
authors.initials: BA
authors.lastname: Nassar
authors.forename: E M
authors.initials: EM
authors.lastname: Zayed
authors.forename: L M
authors.initials: LM
authors.lastname: Title
authors.forename: B J
authors.initials: BJ
authors.lastname: O'Neill
authors.forename: I R
authors.initials: IR
authors.lastname: Bata
authors.forename: S A
authors.initials: SA
authors.lastname: Kirkland
authors.forename: J
authors.initials: J
authors.lastname: Dunn
authors.forename: G I
authors.initials: GI
authors.lastname: Dempsey
authors.forename: M H
authors.initials: MH
authors.lastname: Tan
authors.forename: D E
authors.initials: DE
authors.lastname: Johnstone
mesh_terms: D003327:Coronary Disease / Q000097:blood / Q000235:genetics*; D005260:Female; D005293:Ferritins / Q000097:blood; D006680:HLA Antigens / Q000235:genetics*; D006486:Hemosiderosis / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D007501:Iron / Q000097:blood*; D008297:Male; D009154:Mutation; D012737:Sex Factors
chemical_list: D006680:HLA Antigens; D005293:Ferritins; D007501:Iron