Nahon Pierre, Sutton Angela, Pessayre Dominique, Rufat Pierre, Ziol Marianne, Ganne-Carrie Nathalie, Charnaux Nathalie, Trinchet Jean-Claude, Gattegno Liliane, Beaugrand Michel
Service d'Hépato-Gastroentérologie, Hôpital Jean Verdier, Assistance Publique-Hôpitaux de Paris, Bondy, France.
Clin Gastroenterol Hepatol. 2007 May;5(5):630-5. doi: 10.1016/j.cgh.2006.11.022. Epub 2007 Mar 2.
BACKGROUND & AIMS: A genetic dimorphism encodes for either alanine (Ala) or valine (Val) in the mitochondrial targeting sequence of manganese superoxide dismutase (MnSOD), and modulates its mitochondrial import and activity. It has been shown that the presence of at least 1 Ala-encoding allele is more frequent in alcoholic patients with cirrhosis than in controls, and increases the risks of liver iron overload, hepatocellular carcinoma (HCC), and death in these patients. The aim of this study was to assess the influence of the Ala-9Val MnSOD dimorphism on the same parameters and events in hepatitis C virus (HCV)-infected patients.
We compared the MnSOD genotypic distributions in 94 control subjects and 165 patients with HCV-related cirrhosis. Patients were included at the time of liver biopsy examination showing cirrhosis, and were followed-up prospectively. The mean time of follow-up evaluation was 85.7 +/- 43.8 months.
The distribution of MnSOD genotypes in HCV-infected patients (25% Val/Val homozygotes, 44% Ala/Val heterozygotes, and 31% Ala/Ala homozygotes) did not differ from the distribution in controls (P = .3). MnSOD genotypes did not influence survival (log-rank test, P = .6; relative risk 1.0; 95% confidence interval, 0.6-1.6) or the risk of HCC occurrence (log-rank test, P = .3; relative risk, 1.1; 95% confidence interval, 0.8-1.6).
Contrary to previous findings in French alcoholic patients, the Ala-encoding MnSOD allele is represented equally in controls and patients with HCV-related cirrhosis, and it does not significantly influence the risks of liver iron overload, HCC, or death in these patients.
锰超氧化物歧化酶（MnSOD）的线粒体靶向序列存在一种基因多态性，可编码丙氨酸（Ala）或缬氨酸（Val），并调节其线粒体导入和活性。研究表明，在酒精性肝硬化患者中，至少携带1个编码Ala等位基因的频率高于对照组，且会增加这些患者肝脏铁过载、肝细胞癌（HCC）和死亡的风险。本研究旨在评估丙氨酸-9缬氨酸MnSOD基因多态性对丙型肝炎病毒（HCV）感染患者相同参数和事件的影响。
我们比较了94名对照受试者和165例HCV相关肝硬化患者的MnSOD基因型分布。患者在肝活检显示肝硬化时纳入研究，并进行前瞻性随访。随访评估的平均时间为85.7±43.8个月。
HCV感染患者中MnSOD基因型的分布（25% Val/Val纯合子、44% Ala/Val杂合子和31% Ala/Ala纯合子）与对照组的分布无差异（P = 0.3）。MnSOD基因型不影响生存率（对数秩检验，P = 0.6；相对风险1.0；95%置信区间，0.6 - 1.6）或HCC发生风险（对数秩检验，P = 0.3；相对风险，1.1；95%置信区间，0.8 - 1.6）。
与先前法国酒精性患者的研究结果相反，编码Ala的MnSOD等位基因在对照组和HCV相关肝硬化患者中的比例相同，且对这些患者肝脏铁过载、HCC或死亡风险无显著影响。
