Measurement of serum hepcidin-25 levels as a potential test for diagnosing hemochromatosis and related disorders
Measurement of serum hepcidin-25 levels as a potential test for diagnosing hemochromatosis and related disorders
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DOI：
10.1007/s00535-010-0259-8
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发表时间：
2010-11-01
影响因子：
6.3
通讯作者：
Yamagishi, Masakazu
中科院分区：
文献类型：
--
作者：
Kaneko, Yoshibumi;Miyajima, Hiroaki;Yamagishi, Masakazu
铁超载综合征包括广泛的遗传性和获得性疾病。最近的研究表明，抑制肝脏中海普西丁的合成是血色病的分子基础。然而，后天铁负荷过重的肝脏会合成足够量的海普西丁。因此，海普西丁可以作为鉴别诊断铁超载综合征的生化标志物。我们检测了13例日本铁超载综合征患者的血清铁参数和海普西丁-25水平，并对HFE、HJV、HAMP、TFR2和SLC40A1基因进行了测序。此外，我们还对3名日本患者和4名意大利人的HFE血色沉着症患者进行了用高效液相色谱-串联质谱仪直接测定血清海普西丁-25水平。在13名日本患者中，发现1名HJV血色沉着症患者，2名TFR2血色沉着症患者和3名铁门蛋白病患者。其余7名日本患者没有证据表明铁超载综合征的遗传基础。7例血色素沉着症患者和3例无纤维蛋白溶血酶血症患者的血清海普西丁-25水平明显降低。相比之下，3例铁门蛋白病患者和7例继发性铁超载综合征患者的血清海普西丁水平与他们的高铁蛋白血症平行。铁负荷综合征患者分为两种表型，表现为低和高海人胆碱血症。在进行基因分析之前，检测血清海普西丁-25水平可能有助于铁过载综合征的鉴别诊断。
Iron overload syndromes include a wide spectrum of genetic and acquired conditions. Recent studies suggest suppressed hepcidin synthesis in the liver to be the molecular basis of hemochromatosis. However, a liver with acquired iron overload synthesizes an adequate amount of hepcidin. Thus, hepcidin could function as a biochemical marker for differential diagnosis of iron overload syndromes.We measured serum iron parameters and hepcidin-25 levels followed by sequencing HFE, HJV, HAMP, TFR2, and SLC40A1 genes in 13 Japanese patients with iron overload syndromes. In addition, we performed direct measurement of serum hepcidin-25 levels using liquid chromatography-tandem mass spectrometry in 3 Japanese patients with aceruloplasminemia and 4 Italians with HFE hemochromatosis.One patient with HJV hemochromatosis, 2 with TFR2 hemochromatosis, and 3 with ferroportin disease were found among the 13 Japanese patients. The remaining 7 Japanese patients showed no evidence for genetic basis of iron overload syndrome. As far as the serum hepcidin-25 was concerned, seven patients with hemochromatosis and 3 with aceruloplasminemia showed markedly decreased serum hepcidin-25 levels. In contrast, 3 patients with ferroportin disease and 7 with secondary iron overload syndromes showed serum hepcidin levels parallel to their hyperferritinemia. Patients with iron overload syndromes were divided into 2 phenotypes presenting as low and high hepcidinemia. These were then associated with their genotypes.Determining serum hepcidin-25 levels may aid differential diagnosis of iron overload syndromes prior to genetic analysis.