Interferon reduces somatic mutation of mitochondrial DNA in liver tissues from chronic viral hepatitis patients
Interferon reduces somatic mutation of mitochondrial DNA in liver tissues from chronic viral hepatitis patients
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DOI：
10.1111/j.1365-2893.2005.00623.x
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发表时间：
2005-09-01
影响因子：
2.5
通讯作者：
Inoue, M
中科院分区：
文献类型：
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作者：
Nishikawa, M;Nishiguchi, S;Inoue, M
我们最近报道，遗传不稳定导致非癌肝组织中线粒体DNA（mtDNA）突变率高，这与临床检测到的多中心肝癌发生一致。干扰素（IFN）已被报道可以减少肝炎病毒感染个体的肝癌发生。肝活检标本来自26例慢性丙型肝炎病毒（HCV）感染患者在IFN治疗前后（总剂量：2.52亿单位）。研究人群的平均（+/- SD）年龄为45 ± 9岁，13例（50%）为男性[采集方式：输血（27%），未知（73%）;病毒载量：5.2 ± 1.1 k拷贝/mL;感染持续时间：17 ± 9年（65%），未知（35%）;基因型：I（4%），II（80%），III（8%），IV（8%）;酒精摄入：阳性（31%），阴性（69%）]。从标本中提取DNA样本并进行直接测序。与21名对照组相比，丙型肝炎病毒感染者肝脏标本中D环线粒体DNA突变频率增加（2.5 vs 0.6，P < 0.001）。干扰素治疗可减少线粒体DNA突变（平均差异= 0.7，P < 0.001），且线粒体DNA突变数量的减少与总组织学活动指数评分的抑制呈正相关（平均差异= 1.3，P < 0.01）。这些结果清楚地表明，mtDNA的突变率与IFN治疗密切相关。因此，线粒体DNA的分析可能为IFN的疗效评价提供一个新的标准，并可能有助于预测致癌风险。
We recently reported that the genetic instability resulting in the high rate of mitochondrial DNA (mtDNA) mutation in noncancerous liver tissue is consistent with the multicentric hepatocarcinogenesis detected clinically. Interferon (IFN) has been reported to reduce hepatocarcinogenesis in individuals with hepatitis virus infection. Liver biopsy specimens were obtained from 26 patients with chronic hepatitis C virus (HCV) infection before and after IFN therapy (total dose: 252 million units). The mean (+/- SD) age of the study population was 45 +/- 9 years and 13 (50%) were male [mode of acquisition: blood transfusion (27%), unknown (73%); viral load: 5.2 +/- 1.1 k copies/mL; duration of infection: 17 +/- 9 years (65%), unknown (35%); genotype: I (4%), II (80%), III (8%), IV (8%); alcohol intake: positive (31%), negative (69%)]. DNA samples were extracted from the specimens and subjected to direct sequencing. The mtDNA mutation frequency in the D-loop was increased in liver specimens from individuals with HCV infection compared with 21 controls (2.5 vs 0.6, P < 0.001). IFN therapy decreased the mtDNA mutation (mean difference = 0.7, P < 0.001) and the decreased number of mtDNA mutations was positively correlated with suppression of the total histological activity index score (mean difference = 1.3, P < 0.01). These results clearly indicate that the mutational rate of mtDNA is strongly associated with IFN therapy. Thus, analysis of mtDNA could provide a new criterion for the therapeutic evaluation of the effect of IFN, and may be useful for the prediction of risk of carcinogenesis.