Prevalence of C282Y and H63D mutations in the hemochromatosis (HFE) gene in the United States

JAMA. 2001 May 2;285(17):2216-22. doi: 10.1001/jama.285.17.2216.


Context: Population-based estimates of the prevalence of disease-associated mutations, such as hemochromatosis (HFE) gene mutations, are needed to determine the usefulness of genetic screening.

Objective: To estimate the prevalence of the HFE mutations C282Y and H63D in the US population.

Design: Cross-sectional population-based study of samples in the DNA bank from phase 2 of the Third National Health and Nutrition Examination Survey conducted from 1992 to 1994.

Setting and participants: Genotyped samples of cells from a total of 5171 participants, cross-classified by sex, age, and race/ethnicity in the analysis.

Main outcome measures: Estimates of the prevalence of C282Y and H63D mutations.

Results: The prevalence of C282Y homozygosity is estimated to be 0.26% (95% confidence interval [CI], 0.12%-0.49%); 1.89% (95% CI, 1.48%-2.43%) for H63D homozygosity; and 1.97% (95% CI, 1.54%-2.49%) for compound heterozygosity. The prevalence estimates for C282Y heterozygosity (C282Y/wild type) are 9.54% among non-Hispanic whites, 2.33% among non-Hispanic blacks, and 2.75% among Mexican-Americans. The prevalence estimates of the C282Y mutation in the US population are 5.4% (95% CI, 4.7%-6.2%) and 13.5% (95% CI, 12.5%-14.8%) for the H63D mutation.

Conclusions: Estimates of prevalence of HFE mutations are within the expected range for non-Hispanic whites and blacks but the estimated prevalence of the C282Y mutation among Mexican-Americans is less than expected. Mutation data now need to be linked to clinically relevant indices, such as transferrin saturation level.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Genotype
  • HLA Antigens / genetics*
  • Hemochromatosis / epidemiology*
  • Hemochromatosis / genetics*
  • Hemochromatosis Protein
  • Histocompatibility Antigens Class I / genetics*
  • Humans
  • Membrane Proteins*
  • Mutation, Missense*
  • Nutrition Surveys
  • Prevalence
  • United States / epidemiology


  • HFE protein, human
  • HLA Antigens
  • Hemochromatosis Protein
  • Histocompatibility Antigens Class I
  • Membrane Proteins