Fiel M I, Schiano T D, Bodenheimer H C, Thung S N, King T W, Varma C R, Miller C M, Brunt E M, Starnes S, Prass C, Wolff R K, Bacon B R
Department of Medicine, The Mount Sinai School of Medicine, New York, NY, USA.
Liver Transpl Surg. 1999 Jan;5(1):50-6. doi: 10.1002/lt.500050109.
A candidate gene, HFE, was recently described in patients with hereditary hemochromatosis (HH) and found to contain a missense mutation leading to a cysteine to tyrosine substitution (C282Y). A second mutation, H63D, was also found in the gene. This study was undertaken to determine the HFE genotype in liver transplant recipients clinically diagnosed with HH and those incidentally found to have increased iron deposition in their explanted livers and to evaluate whether biochemical or histological hepatic iron indices (HIIs) correlated with homozygosity for the C282Y mutation. We identified 15 patients clinically diagnosed with various liver disorders other than HH who had increased liver iron deposits among 918 adult patients who underwent liver transplantation from 1988 to 1995. Four additional patients were clinically diagnosed as having HH. Archival explant liver tissue was evaluated for the histological HII according to the method of Deugnier et al, in which an index greater than 0.15 suggests homozygosity for HH. The HII was computed according to established methods, with a value greater than 1.9 suggesting homozygosity for HH. A portion of liver tissue was subjected to DNA genotyping using polymerase chain reaction-amplified products. Two of 4 patients with clinically suspected HH were homozygous for C282Y, and 2 patients had neither mutation. One of the 15 patients not suspected to have HH was a C282Y homozygote, 1 was a C282Y heterozygote, 6 were H63D heterozygotes, and 7 had neither mutation. The histological HII was consistent with HH in 13 patients, whereas the HII was consistent with HH in 6 patients. Thus, in patients with end-stage liver disease, despite fulfilling the established clinical criteria for HH using biochemical and histological parameters, only a minority of patients were homozygous for the C282Y mutation. Hepatic iron overload may result from other causes, and in end-stage liver disease, an elevated HII may not accurately predict HH. Other factors that either control or lead to iron absorption may explain iron overload in these patients.
一个候选基因HFE最近在遗传性血色素沉着症（HH）患者中被发现，该基因包含一个错义突变，导致半胱氨酸被酪氨酸取代（C282Y）。在该基因中还发现了另一个突变H63D。本研究旨在确定临床诊断为HH的肝移植受者以及在其移植肝中偶然发现铁沉积增加的受者的HFE基因型，并评估生化或组织学肝脏铁指标（HIIs）是否与C282Y突变纯合性相关。我们在1988年至1995年接受肝移植的918例成年患者中，确定了15例临床诊断为除HH外的各种肝脏疾病且肝脏铁沉积增加的患者。另外4例患者临床诊断为HH。根据Deugnier等人的方法评估存档的移植肝组织的组织学HII，其中指数大于0.15提示HH纯合性。HII根据既定方法计算，值大于1.9提示HH纯合性。使用聚合酶链反应扩增产物对一部分肝组织进行DNA基因分型。4例临床疑似HH的患者中有2例为C282Y纯合子，2例无突变。15例未怀疑患有HH的患者中，1例为C282Y纯合子，1例为C
