Geographic and Racial/Ethnic Differences in HFE Mutation Frequencies and Iron Phenotypes in the Hemochromatosis and Iron Overload Screening (HEIRS) Study.

Designing an optimal screening approach for hemochromatosis and iron overload requires knowledge of racial/ethnic subpopulations and frequencies of HFE mutations and phenotypes in geographic areas. In the HEIRS Study, HFE C282Y and H63D genotypes and prevalences of participants who met biochemical criteria for further evaluation (transferrin saturation >50% and ferritin >300 ng/mL, men; >45% and >200 ng/mL, women) were compared in a primary care-based sample of ~100,000 adults ≥25 years from 5 Field Centers. There were different respective HFE C282Y and H63D genotype frequencies in Whites, Blacks, Asians, and Hispanics across geographic areas (all p<0.0001), but not in Native Americans or Pacific Islanders. In Whites, the C282Y/C282Y proportion was significantly higher in AL than in CA or OR/HI. AL also had a significantly higher proportion of C282Y/wt than CA or OR/HI. In Blacks, D.C. had a significantly higher proportion of C282Y and H63D genotypes than AL. ONT had a significantly higher H63D genotype proportion than AL. In Asians, CA had a significantly higher proportion of H63D genotypes than OR/HI or ONT. In Hispanics, there were significant differences between: AL and CA; AL and D.C.; CA and D.C.; CA and OR/HI; D.C. and OR/HI; and D.C. and ONT. We also observed:

Prevalences of Participants Who Met Biochemical Criteria for Further Evaluation

The percentage of men who met biochemical criteria for further evaluation was greater than that of women. We conclude that 1) C282Y and H63D genotype frequencies vary significantly within a single racial/ethnic group across geographic regions; and 2) the percentage of participants who met biochemical criteria for further evaluation varies by racial/ethnic group.