Association of myeloperoxidase promotor polymorphism with cirrhosis in patients with hereditary hemochromatosis
Association of myeloperoxidase promotor polymorphism with cirrhosis in patients with hereditary hemochromatosis
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DOI：
10.1016/j.jhep.2005.01.023
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发表时间：
2005-06-01
影响因子：
25.7
通讯作者：
Ferenci, P
中科院分区：
文献类型：
--
作者：
Österreicher, CH;Datz, C;Ferenci, P
背景/目的：遗传性血色素沉着症（HHC）是一种外显率可变的铁代谢紊乱。氧化应激在肝硬化的进展中起着核心作用。一些参与活性氧化剂产生或降解的酶，如髓过氧化物酶 (MPO) 和血红素加氧酶 (HO)-1，会受到启动子多态性的影响。本研究评估了 MPO (-463G/A) 和维也纳 HO-1 启动子 (GT)(n) 多态性对 HHC 患者肝硬化进展的影响。方法：研究了 158 名无纤维化进展辅助因子的 C282Y 纯合子（119 名男性；平均年龄：51.0 +/- 13.3）。所有患者均接受肝活检。通过原子吸收分光光度法测定肝铁含量。通过RFLP分析评估MPO多态性；通过基于激光的半自动 DNA 测序仪进行 HO-1 微卫星多态性分析。结果：MPO 基因型 GG、GA 和 AA 分别在 102 例（64.6%）、45 例和 11 例患者中发现。 GG 基因型在肝硬化患者中比非肝硬化患者更常见（78.7% vs. 55.7%，P = 0.003）。 HO-I基因型的分布没有不同。 Logistic回归分析显示MPO基因型GG、血清铁蛋白、年龄和男性是肝硬化的独立预测因素。结论：MPO基因型GG与遗传性血色素沉着症患者的肝硬化相关。 (C) 2005 年欧洲肝脏研究协会。由 Elsevier B.V. 出版。保留所有权利。
Background/Aims: Hereditary hemochromatosis (HHC) is a disorder of iron metabolism with variable penetrance. Oxidative stress plays a central role in the progression to cirrhosis. Several enzymes involved in the production or degradation of reactive oxidants, like myeloperoxidase (MPO) and heme oxygenase (HO)-1 are influenced by promotor polymorphisms. This study assessed the impact of polymorphisms of the MPO (-463G/A) and the HO-1 promotors of Vienna (GT)(n) on the evolution of cirrhosis in patients with HHC.Methods: One-hundred and fifty-eight C282Y homozygotes without cofactors for fibrosis progression (119 males; mean age: 51.0 +/- 13.3) were studied. All patients underwent liver biopsy. Hepatic iron content was measured by atom absorption spectrophotometry. MPO polymorphism was assessed by RFLP analysis; HO-1 microsatellite polymorphism by a laser-based semi-automated DNA sequencer.Results: The MPO genotypes GG, GA, and AA were found in 102 (64.6%), 45 and 11 patients, respectively. The GG-genotype was more common in patients with cirrhosis than in those without (78.7 vs. 55.7 %, P = 0.003). The distribution of HO-I genotypes was not different. Logistic regression analysis revealed MPO genotype-GG, serum ferritin, age and male sex as independent predictors for cirrhosis.Conclusions: MPO genotype GG is associated with cirrhosis in patients with hereditary hemochromatosis. (C) 2005 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.