Iron Overload in Africa

作者：Victor R. Gordeuk, Joshua M. Mukiibi, Sandra J. Hasstedt, Wade S. Samowitz, Corwin Q. Edwards, G. Alexander West, Solomon Ndambire, Jean Emmanual, Neal Nkanza, Zivanai Cuthbert Chapanduka, Maurice Randall, Paul W. Boone, Paula J. Romano, Robert W. Martell, Toyoko S. Yamashita, Paul V. Effler, Gary M. Brittenham · 发表于：New England Journal of Medicine · 年份：1992 · DOI：10.1056/nejm199201093260204 · 被引用次数：285 · 研究领域：Iron Metabolism and Disorders、Hemoglobinopathies and Related Disorders、Nutrition, Genetics, and Disease

BACKGROUND AND METHODS: In contrast to hemochromatosis, which in white populations is inherited through a gene linked to the HLA locus, iron overload in sub-Saharan Africa is believed to result solely from increased dietary iron derived from traditional home-brewed beer. To examine the hypothesis that African iron overload also involves a genetic factor, we used likelihood analysis to test for an interaction between a gene (the hypothesized iron-loading locus) and an environmental factor (increased dietary iron) that determines transferrin saturation and unsaturated iron-binding capacity. We studied 236 members of 36 African families chosen because they contained index subjects with iron overload. Linkage to the HLA region was tested with use of lod scores. RESULTS: In the index subjects, increased iron was present in both hepatocytes and cells of the mononuclear-phagocyte system. Among family members with increased dietary iron due to the consumption of traditional beer, transferrin saturation in serum was distributed bimodally, with 56 normal values (less than 60 percent saturation) and 44 elevated values; the mean serum ferritin concentration was five times higher in the subjects with elevated transferrin saturation (P less than 0.005). The pedigree analysis provided evidence of both a genetic effect (P less than 0.005) and an effect of increased dietary iron (P less than 0.005) on transferrin saturation and unsaturated iron-binding capacity. In the most likely model, incr...