Molecular studies of liver disease in erythropoietic protoporphyria
Molecular studies of liver disease in erythropoietic protoporphyria
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DOI：
10.1097/01.mcg.0000155518.96629.ea
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发表时间：
2005-04-01
影响因子：
2.9
通讯作者：
Risheg, H
中科院分区：
文献类型：
--
作者：
Bloomer, J;Wang, YM;Risheg, H
目标：本研究的目的是确定红细胞生成性原卟啉症（EPP）肝脏疾病的分子决定因素。背景：EPP是一种遗传性疾病，其中铁螯合酶活性不足导致原卟啉过量产生，并经胆汁排泄。研究：在25个EPP家族中进行了铁螯合酶基因分析，以确定导致低基因表达的突变和多态性（IVS 3 - 48 c）。多个肝脏基因的表达也检查了DNA微阵列分析的患者谁有肝移植，以确定基因改变regulation.Results：杂合铁螯合酶突变被发现在43个人。在31例有症状的患者中，94%的患者（其中15例患有肝脏疾病）中，该多态性也存在于非突变等位基因中。解释肝移植的患者表现出显着的变化，参与伤口愈合，有机阴离子转运，和oxidative stress.Conclusions的几个基因的表达：患者与EPP谁发展肝病通常有一个突变的亚铁螯合酶等位基因，改变酶的功能，连同多态性的nonmutant等位基因，导致低基因表达。这导致原卟啉的肝胆排泄显著增加，其可通过胆汁淤积性损伤和氧化应激两者损害肝脏。
Goals: The goal of this study was to define molecular determinants of liver disease in erythropoietic protoporphyria (EPP).Background: EPP is a genetic disorder in which deficient ferrochelatase activity causes excessive production of protoporphyrin, which is excreted in bile. Some patients develop liver disease that necessitates transplantation.Study: Ferrochelatase gene analysis was done in 25 families with EPP to identify mutations and a polymorphism (IVS3-48c) that causes low gene expression. Expression of multiple hepatic genes was also examined by DNA microarray analysis in patients who had liver transplantation to identify genes with altered regulation.Results: Heterozygous ferrochelatase mutations were found in 43 individuals. In 94% of 31 symptomatic patients, 15 of whom had liver disease, the polymorphism was also present in the nonmutant allele. Explained liver of patients who had transplantation showed significant change in expression of several genes involved in wound healing, organic anion transport, and oxidative stress.Conclusions: Patients with EPP who develop liver disease usually have a mutation in one ferrochelatase allele that alters enzyme function, together with a polymorphism in the nonmutant allele that causes low gene expression. This results in significant increase in the hepatobiliary excretion of protoporphyrin, which can damage the liver through both cholestatic injury and oxidative stress.