Prevalence of coronary heart disease associated with HFE mutations in adults attending a health appraisal center

Am J Med. 2002 Oct 15;113(6):472-9. doi: 10.1016/s0002-9343(02)01249-4.


Purpose: Mutations of the HFE gene that cause hereditary hemochromatosis may be associated with an increased risk of cardiovascular disease. We examined the relation between two HFE mutations (C282Y and H63D), indicators of iron homeostasis, and the prevalence of coronary heart disease in a large population of white adults.

Subjects and methods: We conducted a cross-sectional study of 30,916 white adults aged 25 to 98 years who attended a health appraisal center and underwent screening for HFE mutations. Coronary heart disease and cardiovascular risk factors were ascertained by questionnaire and medical records.

Results: Overall, 12% (1798/15,362) of men and 7% (1074/15,554) of women had a history of coronary heart disease. Of 10 HFE genotypes tested (five genotypes by sex), only men with the C282Y/H63D genotype (compound heterozygotes) had a significantly higher prevalence of coronary heart disease compared with men with no HFE mutations (odds ratio = 1.6; 95% confidence interval: 1.1 to 2.4; P = 0.01) after adjusting for cardiovascular risk factors. Elevated serum ferritin levels (>250 ng/mL) were associated with a lower prevalence of coronary heart disease in men (10% [255/2209] vs. 12% [1515/12,461] in controls, P = 0.008), which was not significant after adjusting for use of aspirin and anticoagulants. There were no significant associations between elevated transferrin saturation in either men or women, or between elevated serum ferritin levels or HFE mutations in women, and the prevalence of coronary heart disease.

Conclusion: The results do not support a consistent association between HFE mutations or serum iron indicators and the prevalence of coronary heart disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Coronary Disease / blood
  • Coronary Disease / genetics*
  • Cross-Sectional Studies
  • Female
  • Ferritins / blood
  • Genotype
  • Hemochromatosis / genetics
  • Hemochromatosis Protein
  • Heterozygote
  • Histocompatibility Antigens Class I / genetics*
  • Homozygote
  • Humans
  • Iron / blood
  • Male
  • Membrane Proteins / genetics*
  • Middle Aged
  • Mutation*
  • Risk Factors
  • Transferrin / analysis


  • HFE protein, human
  • Hemochromatosis Protein
  • Histocompatibility Antigens Class I
  • Membrane Proteins
  • Transferrin
  • Ferritins
  • Iron