Hemochromatosis is a cosmopolitan group of disorders characterized by increased absorption of dietary iron,, increased risk of iron overload (IO) with consequent tissue injury, and inappropriately low levels of hepcidin, the central controller of iron absorption. In 1996, it was discovered that the most common hemochromatosis subtype is due to homozygosity for the p.C282Y allele (exon 4, c.845G>A; rs1800562) of HFE (homeostatic iron regulator, chromosome 6p22.2). Most p.C282Y homozygotes are whites who reside in western Europe and derivative countries including Australia, Canada, and the U.S. , Typical hemochromatosis laboratory phenotypes of untreated adults with HFE p.C282Y homozygosity include elevated transferrin saturation (TS), elevated serum ferritin (SF) levels, and increased iron in hepatocytes. Complications of IO occur in some patients with p.C282Y homozygosity, including arthropathy, diabetes, hypogonadism, elevated serum concentrations of hepatic transaminases, hepatic fibrosis, and cirrhosis. IO also occurs in some persons with p.C282Y in compound heterozygosity with HFE p.H63D (exon 2, c.187C>G, rs1799945). A 1991 report described an African-American man with hemochromatosis, severe hepatocyte iron loading, cirrhosis, and human leukocyte antigens A*03 and B*07 suggestive of HFE hemochromatosis. In 2001-2005, there were reports of referred African-American patients with hemochromatosis phenotypes who had either HFE p.C282Y homozygosity or p.C282Y/p.H63D compound heterozygosity. , In 27,124 self-identified black participants in a primary care-based North American hemochromatosis and iron overload screening study, the prevalence of HFE p.C282Y homozygosity was 0.00011. In the same cohort, the prevalence of p.C282Y/p.H63D compound heterozygosity was 0.0013.
There is no reported prevalence estimate of IO in African Americans (AA) with hemochromatosis-associated HFE genotypes, without or with IO-related disease.
We sought to estimate the prevalences and numbers of African-American men and women with hemochromatosis-associated HFE genotypes who have IO without and with IO-related disease. We compiled reports of the prevalences of hemochromatosis-associated HFE genotypes p.C282Y/p.C282Y and p.C282Y/p.H63D in AA using data from population and cohort studies identified by computerized searches of medical literature. We computed numbers of African-American men and women ≥18 y using 2018 U.S. Census estimates. We estimated numbers of African-American men and women with IO without and with IO-related disease using proportions of whites of European ancestry with IO without and with IO-related disease in population studies and classified by hemochromatosis-associated HFE genotypes. We discuss the relative contribution of HFE genotypes to non-transfusion IO in AA.a