Prevalence of C282Y and H63D Mutations in the Hemochromatosis (HFE) Gene in the United States

• Published in: JAMA : the journal of the American Medical Association 2001-05, Vol.285 (17), p.2216-2222
• Main Authors: Steinberg, Karen K, Cogswell, Mary E, Chang, Joy C, Caudill, Samuel P, McQuillan, Geraldine M, Bowman, Barbara A, Grummer-Strawn, Laurence M, Sampson, Eric J, Khoury, Muin J, Gallagher, Margaret L
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Estimates; Genes; Genotype; Hemochromatosis - epidemiology; Hemochromatosis - genetics; Hemochromatosis Protein; Histocompatibility Antigens Class I - genetics; HLA Antigens - genetics; Humans; Investigative techniques, diagnostic techniques (general aspects); Medical sciences; Medical screening; Membrane Proteins; Metabolic diseases; Mutation; Mutation, Missense; Nutrition Surveys; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Prevalence; United States - epidemiology
• ISSN: 0098-7484; 1538-3598
• 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.