Prevalence of CY282Y and H63D mutations in the hemochromatosis (HFE) gene in the United States

Context Population-based estimates of the prevalence of disease-associated mutations. such as hemochromatosis (HFE) gene mutations, are needed to dete rmine 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 fr om phase 2 of the Third National Health and Nutrition Examination Survey co nducted from 1992 to 1994. Setting and Participants Genotyped samples of cells from a total of 5171 pa rticipants, cross-classified by sex, age, and race/ethnicity in the analysi s. Main Outcome Measures Estimates of the prevalence of C282Y and H63D mutatio ns. 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 H63 D 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 expecte d 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 transfer rin saturation level.