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Karen K. Steinberg, PhD; Mary E. Cogswell, DrPH; Joy C. Chang, PhD; Samuel P. Caudill, PhD; Geraldine M. McQuillan, PhD; Barbara A. Bowman, PhD; Laurence M. Grummer-Strawn, DrPH; Eric J. Sampson, PhD; Muin J. Khoury, MD,PhD; Margaret L. Gallagher, PhD

JAMA. 2001;285:2216-2222.

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.

Author Affiliations: Division of Laboratory Sciences (Drs Steinberg, Chang, Caudill, Sampson, and Gallagher), Office of Genetics and Disease Prevention (Dr Khoury), National Center for Environmental Health, and Divisions of Nutrition and Physical Activity (Drs Cogswell and Grummer-Strawn) and Diabetes Translation (Dr Bowman), National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Chamblee, Ga; and Division of Health Examination Statistics, National Center for Health Statistics, Centers for Disease Control and Prevention, Rockville, Md (Dr McQuillan).

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