Gordeuk V, Mukiibi J, Hasstedt S J, Samowitz W, Edwards C Q, West G, Ndambire S, Emmanual J, Nkanza N, Chapanduka Z
University of Zimbabwe School of Medicine, Harare.
N Engl J Med. 1992 Jan 9;326(2):95-100. doi: 10.1056/NEJM199201093260204.
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.
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, increased dietary iron raised the mean transferrin saturation from 30 to 81 percent and lowered the mean unsaturated iron-binding capacity from 38 to 13 mumol per liter in subjects heterozygous for the iron-loading locus. The hypothesis of tight linkage to HLA was rejected.
Iron overload in Africa may be caused by an interaction between the amount of dietary iron and a gene distinct from any HLA-linked gene.
与白种人中通过与HLA位点相关基因遗传的血色素沉着症不同，撒哈拉以南非洲地区的铁过载被认为完全是由传统家酿啤酒中增加的膳食铁所致。为检验非洲铁过载也涉及遗传因素这一假说，我们采用似然分析来检测一个基因（假定的铁负荷位点）与一个环境因素（增加的膳食铁）之间的相互作用，该环境因素决定转铁蛋白饱和度和不饱和铁结合能力。我们研究了36个非洲家庭的236名成员，这些家庭因包含铁过载的索引对象而被选中。使用连锁分数对与HLA区域的连锁进行了检测。
在索引对象中，肝细胞和单核吞噬细胞系统的细胞中均存在铁增加。在因饮用传统啤酒而膳食铁增加的家庭成员中，血清转铁蛋白饱和度呈双峰分布，56个为正常数值（饱和度低于60%），44个为升高数值；转铁蛋白饱和度升高的受试者血清铁蛋白平均浓度高出五倍（P<0.005）。系谱分析提供了遗传效应（P<0.005）和膳食铁增加对转铁蛋白饱和度及不饱和铁结合能力的影响（P<0.005）的证据。在最可能的模型中，对于铁负荷位点杂合的受试者，增加的膳食铁使平均转铁蛋白饱和度从30%提高到81%，并使平均不饱和铁结合能力从38μmol/L降低到13μmol/L。与HLA紧密连锁的假说被否定。
非洲的铁过载可能是由膳食铁量与一个不同于任何与HLA相关基因的基因之间的相互作用引起的。
