Sampietro M, Piperno A, Lupica L, Arosio C, Vergani A, Corbetta N, Malosio I, Mattioli M, Fracanzani A L, Cappellini M D, Fiorelli G, Fargion S
Istituto di Medicina Interna e Fisiopatologia Medica, Università di Milano and IRCCS Ospedale Maggiore, Italy.
Hepatology. 1998 Jan;27(1):181-4. doi: 10.1002/hep.510270128.
Sporadic porphyria cutanea tarda (PCT) is caused by a reduced activity of uroporphyrinogen decarboxylase (URO-D) in the liver. Mild to moderate iron overload is common in PCT, as iron is one of the factors which trigger the clinical manifestations of the disease through the inactivation of URO-D. A role for genetic hemochromatosis in the development of iron overload in sporadic PCT has been hypothesized in the past. The aim of this work was to investigate whether mutations of HFE, which is a candidate gene for hemochromatosis, play the role of genetic susceptibility factors for PCT in Italian patients, who have a high prevalence of acquired triggering factors, such as hepatitis C virus (HCV) chronic infection and alcohol. We determined HFE genotypes of 68 male patients with PCT. Our data do not confirm an association of PCT with the Cys282Tyr HFE mutation, strongly associated with hemochromatosis in Northern European countries. A second mutation of HFE, His63Asp, however, had a significantly increased frequency as it was present in half of the patients. Surprisingly, the presence of the His63Asp mutation was not related to the iron status of patients, suggesting that a subtle abnormality of iron metabolism induced by this mutation could escape detection by the standard parameters of iron status. In PCT patients with liver disease, the presence of the mutation could contribute to the inactivation of URO-D, either directly or through a synergistic action with other factors that cause liver damage.
散发性迟发性皮肤卟啉症（PCT）是由肝脏中尿卟啉原脱羧酶（URO-D）活性降低引起的。轻度至中度铁过载在PCT中很常见，因为铁是通过使URO-D失活从而引发该疾病临床表现的因素之一。过去曾推测遗传性血色素沉着症在散发性PCT铁过载的发生中起作用。这项工作的目的是研究血色素沉着症候选基因HFE的突变是否在意大利患者中起到PCT遗传易感性因素的作用，这些患者中获得性触发因素如丙型肝炎病毒（HCV）慢性感染和酒精的患病率很高。我们测定了68例男性PCT患者的HFE基因型。我们的数据并未证实PCT与Cys282Tyr HFE突变有关，该突变在北欧国家与血色素沉着症密切相关。然而，HFE的第二个突变His63Asp的频率显著增加，因为有一半的患者存在该突变。令人惊讶的是，His63Asp突变的存在与患者的铁状态无关，这表明该突变诱导的铁代谢细微异常可能无法通过铁状态的标准参数检测到。在患有肝病的PCT患者中，该突变的存在可能直接或通过与其他导致肝损伤的因素协同作用导致URO-D失活。
