Non-alcoholic steatohepatitis and iron: increased prevalence of mutations of the HFE gene in non-alcoholic steatohepatitis
Non-alcoholic steatohepatitis and iron: increased prevalence of mutations of the HFE gene in non-alcoholic steatohepatitis
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DOI：
10.1016/s0168-8278(99)80032-4
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发表时间：
1999-09-01
影响因子：
25.7
通讯作者：
Banner, BF
中科院分区：
文献类型：
--
作者：
Bonkovsky, HL;Jawaid, Q;Banner, BF
背景/目标：非酒精性脂肪性肝炎（NASH）越来越受到重视，其发病机制被认为与氧化应激增加有关。在NASH患者中经常观察到血清铁蛋白水平升高和肝铁染色阳性，并且铁引起的肝损伤的发病机制也被认为涉及氧化应激。本研究的目的是确定是否有NASH和突变的HFE基因相关的遗传性血色病（HHC）的关联。方法：临床，实验室和组织病理学数据的所有57名受试者与NASH的最终诊断之间看到1990年8月和1997年8月在我们的肝脏中心进行了分析。36名患有NASH的白人受试者（23名男性）接受了HFE基因突变的突变分析。将HFE基因突变的患病率与348名白人正常对照进行比较。数据进行了分析，参数和非参数的方法与类似的results.Results：一个主题（2.8%）与NASH是纯合子的C282 Y突变和6（16.7%）纯杂合子，相比，0%和11.2%，分别控制。2例（5.6%）NASH受试者为H63 D突变纯合型，16例（44.4%）为杂合型，而对照组中分别有2.9%和26.4%具有这些基因型。NASH受试者中任一突变的杂合性患病率（61.1%）显著高于对照组（38%）（p=0.008），NASH受试者中纯合性或杂合性组合的患病率（69.4%）显著高于对照组（40.5%，p=0.001）。在有或没有HFE突变的人群中，NASH诊断时的性别（63-67%为男性）和年龄没有差异，但NASH男性患者比女性患者更有可能发生H63 D突变（15/23 vs. 3/13，p
Background/Aims: Non-alcoholic steatohepatitis (NASH) is increasingly recognized, and its pathogenesis is believed to involve increased oxidative stress. Elevated levels of serum ferritin and positive liver iron stains are often observed in patients with NASH, and the pathogenesis of liver injury due to iron is also thought to involve oxidative stress. The aim of this study was to determine whether there is an association of NASH and mutations in the HFE gene associated with hereditary hemochromatosis (HHC).Methods: clinical, laboratory and histopathological data on all 57 subjects with a final diagnosis of NASH seen between August 1990 and August 1997 at our Liver Center were analyzed. Thirty-six Caucasian subjects (23 men) with NASH underwent mutational analyses of HFE gene mutations performed. The prevalence of HFE gene mutations was compared to that in 348 Caucasian normal controls. Data were analyzed by both parameteric and non-parametric methods with similar results.Results: One subject (2.8%) with NASH was homozygous for the C282Y mutation and six (16.7%) mere heterozygous, compared with 0% and 11.2%, respectively, of controls. Two (5.6%) subjects with NASH were homozygous for the H63D mutation and 16 (44.4%) were heterozygous, whereas 2.9% and 26.4%, respectively, of controls had these genotypes. The prevalence of heterozygosity (61.1%) for either mutation was significantly higher in subjects with NASH than in controls (38%) (p=0.008), and the prevalence of homozygosity or heterozygosity combined in NASH subjects (69.4%) was significantly higher than for controls (40.5%, p=0.001). Sex (63-67% male) and age at diagnosis of NASH did not differ between those with or without HFE mutations, but men with NASH were significantly more likely than women to have the H63D mutation (15/23 vs. 3/13, p