Barton James C, Acton Ronald T, Rivers Charles A, Bertoli Luigi F, Gelbart Terri, West Carol, Beutler Ernest
Southern Iron Disorders Center, G-105, 20220 Brookwood Medical Center Drive, Birmingham, AL 35209, USA.
Blood Cells Mol Dis. 2003 Nov-Dec;31(3):310-9. doi: 10.1016/s1079-9796(03)00166-9.
Primary iron overload may be relatively common in African Americans, but its cause is incompletely understood. Thus, we evaluated genotype and phenotype characteristics of unselected African American index patients with primary iron overload who reside in central Alabama. All had hepatic iron concentration > or =30 micromol/g dry wt or > or =2.0 g of iron mobilized by phlebotomy to achieve iron depletion. Genotype analyses were performed in African American control subjects from the same region. There were 23 patients (19 men, 4 women); mean age at diagnosis was 52 +/- 12 years (1 SD) (range 32-69 years). Nine (39.1%) reported that they consumed > or =45 g of ethanol daily; five had chronic hepatitis C. Eight had some form of hemoglobinopathy or thalassemia. Mean serum transferrin saturation was 56 +/- 28% (range 15-100%). The geometric mean serum ferritin at diagnosis was 1076 ng/mL [95% confidence interval 297-3473 ng/mL]. Increased stainable liver iron was observed in hepatocytes only in 4 patients, in macrophages only in 8 patients, and in hepatocytes and macrophages in 8 patients. The mean quantity of iron mobilized by phlebotomy (corrected for iron absorbed during treatment) was 5.3 +/- 2.0 g (range 4.0-8.4 g). Iron removed by phlebotomy was greater in patients with hemoglobinopathy or thalassemia than in those without these forms of anemia (6.6 +/- 1.3 g vs 3.9 +/- 1.6 g, respectively; P = 0.0144). Daily consumption of > or =45 g of ethanol or chronic hepatitis C was not associated with an increased or decreased amount of phlebotomy-mobilized iron, on the average. The percentage of index patients positive for HFE C282Y was greater than that of controls (P = 0.0058). The respective percentages of phenotype positivity for HFE H63D, D6S105(8), and HLA-A*03 were similar in patients and controls. HFE S65C, I105T, and G93R were not detected in index or control subjects. Two of 13 patients were heterozygous for the ferroportin allele nt 744 G-->T (Q248H), although the phenotype frequency of this allele was similar in patients and 39 controls. Synonymous ferroportin alleles were also detected in some patients. The ceruloplasmin mutation nt 1099C-->T (exon 6; Arg367Cys) was detected in 1 of 2 patients tested. Abnormal alleles of beta-2 microglobulin, Nramp2, TFR2, hepcidin, or IRP2 alleles were not detected in either of the 2 patients so tested. We conclude that primary iron overload in African Americans is not the result of the mutation of a single gene. HFE C282Y, ferroportin 744 G-->T, and common forms of heritable anemia appear to account for increased iron absorption or retention in some patients.
原发性铁过载在非裔美国人中可能相对常见，但其病因尚未完全明确。因此，我们评估了居住在阿拉巴马州中部、未经挑选的原发性铁过载非裔美国索引患者的基因型和表型特征。所有患者的肝铁浓度均≥30微摩尔/克干重，或通过静脉放血动员出≥2.0克铁以实现铁耗竭。对来自同一地区的非裔美国对照受试者进行了基因型分析。共有23例患者（19例男性，4例女性）；诊断时的平均年龄为52±12岁（标准差1）（范围32 - 69岁）。9例（39.1%）报告每日乙醇摄入量≥45克；5例患有慢性丙型肝炎。8例患有某种形式的血红蛋白病或地中海贫血。平均血清转铁蛋白饱和度为56±28%（范围15 - 100%）。诊断时血清铁蛋白的几何平均值为1076纳克/毫升[95%置信区间297 - 3473纳克/毫升]。仅在4例患者的肝细胞中观察到可染色肝铁增加，仅在8例患者的巨噬细胞中观察到，在8例患者的肝细胞和巨噬细胞中均观察到。静脉放血动员出的铁的平均量（校正治疗期间吸收的铁）为5.3±2.0克（范围4.0 - 8.4克）。患有血红蛋白病或地中海贫血的患者通过静脉放血去除的铁比未患这些贫血形式的患者更多（分别为6.6±1.3克和3.9±1.6克；P = 0.0144）。平均而言，每日乙醇摄入量≥45克或慢性丙型肝炎与静脉放血动员出的铁量增加或减少无关。索引患者中HFE C282Y阳性的百分比高于对照组（P = 0.0058）。患者和对照组中HFE H63D、D6S105(8)和HLA - A*03表型阳性的各自百分比相似。在索引患者或对照受试者中未检测到HFE S65C、I105T和G93R。13例患者中有2例为铁转运蛋白等位基因nt 744 G→T（Q248H）杂合子，尽管该等位基因的表型频率在患者和39例对照中相似。在一些患者中也检测到了同义铁转运蛋白等位基因。在2例检测的患者中，有1例检测到铜蓝蛋白突变nt 1099C→T（外显子6；Arg367Cys）。在这2例检测的患者中，均未检测到β2微球蛋白、Nramp2、TFR2、铁调素或IRP2等位基因的异常等位基因。我们得出结论，非裔美国人的原发性铁过载并非单个基因突变的结果。HFE C282Y、铁转运蛋白744 G→T以及常见形式的遗传性贫血似乎在一些患者中导致了铁吸收或潴留增加。
