Inheritance of two HFE mutations in African Americans:: Cases with hemochromatosis phenotypes and estimates of hemochromatosis phenotype frequency

Purpose: Two unrelated African Americans had hemochromatosis phenotypes and genotypes. We sought to identify origins of their HFE mutations and estimate frequencies of similar cases. Methods: HFE and HLA genotyping were performed in index cases and family members. HFE genotypes of 1,373 African American controls in five regions were tabulated. Results: Index cases had C282Y/C282Y and C282Y/H63D, respectively; each corresponding Ch6p was likely of Caucasian origin. In controls, frequencies of hemochromatosis-associated genotypes were as follows: C282Y/C282Y, 0.00011; C282Y/H63D, 0.00067; and H63D/H63D, 0.00101. Conclusions: Penetrance-adjusted estimates indicate that similar to9 African Americans per 100,000 have a hemochromatosis phenotype and two common HFE mutations. Hemochromatosis-associated genotype frequencies varied 11.7-fold across regions.