Barton J C, Harmon L, Rivers C, Acton R T
Department of Medicine, Brookwood Medical Center, Birmingham, Alabama 35209, USA.
Blood Cells Mol Dis. 1996;22(3):195-204. doi: 10.1006/bcmd.1996.0100.
We postulated that the severity of iron overload in homozygous hemochromatosis probands is related to the expression of HLA-A3 or D6S105 allele 8. Therefore, we used these markers to characterize Alabama hemochromatosis probands and normal control subjects. We then quantified the blood removed by phlebotomy to exhaust body iron stores and maintain normal serum ferritin concentrations in our hemochromatosis probands. Induction and maintenance phlebotomy requirements were significantly greater in presumed HLA-A3 homozygotes or in D6S105 allele 8 homozygotes than in homozygous probands lacking these markers. Intermediate values were observed in probands who were HLA-A3 or allele 8 heterozygotes, respectively. We also analyzed data from males and females separately. Among subjects of the same sex, the induction and maintenance phlebotomy requirements in subjects presumed to be HLA-A3 homozygotes or in allele 8 homozygotes were greater than those of other groups. Our results support the hypothesis that the severity of iron overload in hemochromatosis is determined predominantly by genetic factors, and provide evidence that two or more mutations for hemochromatosis exist. However, the design of our study does not permit a distinction to be made between allelic and locus heterogeneity for the hemochromatosis gene(s).
我们推测，纯合子血色素沉着症先证者中铁过载的严重程度与HLA - A3或D6S105等位基因8的表达有关。因此，我们使用这些标记来对阿拉巴马州血色素沉着症先证者和正常对照者进行特征分析。然后，我们对通过放血去除的血液进行定量，以耗尽我们血色素沉着症先证者体内的铁储备并维持正常的血清铁蛋白浓度。推测的HLA - A3纯合子或D6S105等位基因8纯合子的诱导和维持放血需求量显著高于缺乏这些标记的纯合子先证者。在分别为HLA - A3或等位基因8杂合子的先证者中观察到中间值。我们还分别分析了男性和女性的数据。在同性别的受试者中，推测为HLA - A3纯合子或等位基因8纯合子的受试者的诱导和维持放血需求量高于其他组。我们的结果支持血色素沉着症中铁过载的严重程度主要由遗传因素决定这一假设，并提供证据表明存在两种或更多种血色素沉着症突变。然而，我们研究的设计不允许区分血色素沉着症基因的等位基因异质性和基因座异质性。
