title: Haemochromatosis mutations and ferritin in myocardial infarction: a case-control study.
abstract: BACKGROUND
  Iron accumulation may contribute to coronary heart disease by catalysing free radical formation and promoting oxidation of low-density lipoprotein cholesterol. Epidemiological studies of iron status and coronary heart disease are conflicting.
  
  
  METHODS
  To test whether genetic haemochromatosis is associated with myocardial infarction, we determined the prevalence of three mutations in the HFE gene (Cys282Tyr, His63Asp and Ser65Cys) in a 2 : 1 case-control study including 177 patients who survived an acute myocardial infarction and 89 controls. Genotypes were determined by PCR amplification of genomic DNA followed by restriction enzyme digestion. We also studied the relationship between plasma ferritin and myocardial infarction.
  
  
  RESULTS
  The carrier frequencies of these three mutations were not statistically different among patients and controls (Cys282Tyr: 1.4 vs. 10.1%; His63Asp: 26.5 vs. 31.5%; Ser65Cys: 2.8 vs. 1.1%). Mean ferritin levels were elevated among patients (176 +/- 155 microg L(-1)) compared with controls (131 +/- 106 microg L(-1), P = 0.015). Subjects with plasma ferritin concentrations of 300 microg L(-1) or more had a 2.9-fold (95% CI: 1.2-7.3, P = 0.02) unadjusted risk for a myocardial infarction compared with those with normal levels. In a univariate analysis, ferritin was significantly associated with myocardial infarction. Upon multiple regression analysis adjusting for smoking, hypertension, diabetes, body-mass index and total cholesterol, significance was no longer present.
  
  
  CONCLUSIONS
  No direct association was found between genetic haemochromatosis and myocardial infarction among Swiss whites. Raised ferritin levels among patients suggest a role of increased iron stores in myocardial infarction, but iron overload was not an independent risk factor for Swiss coronary heart disease patients.
authors.affiliation: Swiss Heart Center, Thrombosis Research Laboratory, Kinder Klinik G4, University Hospital Bern, CH-3010 Bern, Switzerland. dirk.claeys@dkf2.unibe.ch
authors.forename: Dirk
authors.initials: D
authors.lastname: Claeys
authors.forename: M
authors.initials: M
authors.lastname: Walting
authors.forename: F
authors.initials: F
authors.lastname: Julmy
authors.forename: W A
authors.initials: WA
authors.lastname: Wuillemin
authors.forename: B J
authors.initials: BJ
authors.lastname: Meyer
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D005260:Female; D005293:Ferritins / Q000097:blood*; D006680:HLA Antigens / Q000235:genetics; D006432:Hemochromatosis / Q000097:blood / Q000453:epidemiology* / Q000235:genetics*; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006801:Humans; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000453:epidemiology* / Q000235:genetics*; D017354:Point Mutation; D015995:Prevalence; D012307:Risk Factors; D013557:Switzerland / Q000453:epidemiology
chemical_list: C103673:HFE protein, human; D006680:HLA Antigens; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D005293:Ferritins