Myeloperoxidase and Superoxide Dismutase 2 Polymorphisms Comodulate the Risk of Hepatocellular Carcinoma and Death in Alcoholic Cirrhosis
Myeloperoxidase and Superoxide Dismutase 2 Polymorphisms Comodulate the Risk of Hepatocellular Carcinoma and Death in Alcoholic Cirrhosis
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DOI：
10.1002/hep.23187
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发表时间：
2009-11-01
期刊：
影响因子：
13.5
通讯作者：
Beaugrand, Michel
中科院分区：
文献类型：
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作者：
Nahon, Pierre;Sutton, Angela;Beaugrand, Michel
酒精增加肝细胞线粒体中活性氧（ROS）的形成，并通过减少枯否细胞和肝脏浸润中性粒细胞中的烟酰胺腺嘌呤二核苷酸磷酸氧化酶和髓过氧化物酶（MPO）。锰超氧化物歧化酶（MnSOD）将超氧阴离子转化为过氧化氢，除非被谷胱甘肽过氧化物酶或过氧化氢酶（CAT）解毒，否则可以与铁形成羟基自由基。我们的目的是确定Ala 16 Val-超氧化物歧化酶2（SOD 2），G-463 A-MPO或T-262 C-CAT二型性是否调节酒精性肝硬化中肝细胞癌（HCC）和死亡的风险。对190例前瞻性随访的酒精性肝硬化患者的基因型和肝铁评分进行了评估。在随访期间（61.1 ± 2.7个月），51例患者发生HCC，71例死亡。T-262 C-CAT二型性不改变肝铁、HCC或死亡。GG-MPO基因型没有改变铁，但增加了肝癌和死亡的风险。HCC的风险比（HR）为4.7（2.1-10.1），死亡的风险比为3.6（1.9-6.7）。携带一个或两个Ala-SOD 2等位基因与较高的肝脏铁评分和较高的HCC和死亡风险相关。在同时具有GG-MPO基因型和一个或两个Ala-SOD 2等位基因的患者中，HCC的5年发病率为34.4%，仅具有这两个特征之一的患者为5.1%，不具有这些特征的患者为0%。相应的5年死亡率分别为37.6%、11.6%和5%。结论：GG-MPO基因型（导致高MPO表达）和至少一个Ala-SOD 2等位基因（与高肝脏铁评分相关）的组合显著增加了酒精性肝硬化患者发生HCC和死亡的风险。（《肝脏学》2009年;50：1484-1493）
Alcohol increases reactive oxygen species (ROS) formation in hepatocyte mitochondria and by reduced nicotinamide adenine dinucleotide phosphate oxidases and myeloperoxidase (MPO) in Kupffer cells and liver-infiltrating neutrophils. Manganese superoxide dismutase (MnSOD) converts superoxide anion into hydrogen peroxide, which, unless detoxified by glutathione peroxidase or catalase (CAT), can form the hydroxyl radical with iron. Our aim was to determine whether Ala16Val-superoxide dismutase 2 (SOD2), G-463A-MPO, or T-262C-CAT dimorphisms modulate the risks of hepatocellular carcinoma (HCC) and death in alcoholic cirrhosis. Genotypes and the hepatic iron score were assessed in 190 prospectively followed patients with alcoholic cirrhosis. During follow-up (61.1 +/- 2.7 months), 51 patients developed HCC, and 71 died. The T-262C-CAT dimorphism did not modify hepatic iron, HCC, or death. The GG-MPO genotype did not modify iron but increased the risks of HCC and death. The hazard ratio (HR) was 4.7 (2.1-10.1) for HCC and 3.6 (1.9-6.7) for death. Carriage of one or two Ala-SOD2 allele(s) was associated with higher liver iron scores and higher risks of HCC and death. The 5-year incidence of HCC was 34.4% in patients with both the GG-MPO genotype and one or two Ala-SOD2 alleles, 5.1% in patients with only one of these two traits, and 0% in patients with none of these traits. Corresponding 5-year death rates were 37.6%, 11.6%, and 5%. Conclusion: The combination of the GG-MPO genotype (leading to high MPO expression) and at least one Ala-SOD2 allele (associated with high liver iron score) markedly increased the risks of HCC occurrence and death in patients with alcoholic cirrhosis. (HEPATOLOGY 2009;50:1484-1493.)