Kamfar Sharareh, Alavian Seyed Moayed, Houshmand Massoud, Yadegarazari Reza, Seifi Zarei Bahram, Khalaj Alireza, Shabab Noshin, Saidijam Massoud
Department of Molecular Medicine and Genetics, School of Medicine, Hamadan University of Medical Sciences, Hamadan, IR Iran; Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, IR Iran.
Baqiyatallah Research Center for Gastroenterology and Liver Diseases (BRCGL), Baqiyatallah University of Medical Sciences, Tehran, IR Iran; Middle East Liver Diseases (MELD) Center, Tehran, IR Iran.
Hepat Mon. 2016 Nov 9;16(12):e40774. doi: 10.5812/hepatmon.40774. eCollection 2016 Dec.
There is growing evidence that deficiencies observed in the mitochondrial DNA (mtDNA) functions could play an important role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). We hypothesized that genetic variations in mtDNA could affect the mitochondrial function and contribute to the NAFLD susceptibility.
In this study, the possible association of the mtDNA copy number and 4,977-bp deletion levels with NAFLD susceptibility in a sample of Iranian population was evaluated.
This case-control study included 43 NAFLD patients and 20 control subjects. Genomic DNA was extracted from fresh liver tissue samples by using a DNA isolation kit. The mtDNA copy number and mtDNA deletion levels were measured by quantitative real-time PCR and multiplex PCR.
The relative expression of mtDNA copy number was 3.7 fold higher in NAFLD patients than healthy controls (P < 0.0001). The results remained significant after adjustment for age, BMI, and gender (P = 0.02). In addition, the mtDNA copy number was 4.3 (P < 0.0001) and 3.2-fold (P < 0.0001) higher in nonalcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH) patients than healthy controls, respectively. Finally, the results showed that the 4,977-bp deletion is not detected in any of liver tissue samples obtained from the 20 control subjects whereas 8 out of 43 NAFLD patients (18.6%) showed the 4,977 -bp deletion in their liver tissues (P = 0.039).
This study indicated an association between mtDNA content in the liver tissue and NAFLD susceptibility that may be a consequence of compensatory response to the cumulative exposures to oxidative damage.
越来越多的证据表明，线粒体DNA（mtDNA）功能缺陷可能在非酒精性脂肪性肝病（NAFLD）的发病机制中起重要作用。我们推测，mtDNA的基因变异可能影响线粒体功能，并导致NAFLD易感性增加。
在本研究中，评估了伊朗人群样本中mtDNA拷贝数和4977bp缺失水平与NAFLD易感性之间的可能关联。
本病例对照研究纳入了43例NAFLD患者和20例对照受试者。使用DNA分离试剂盒从新鲜肝组织样本中提取基因组DNA。通过定量实时PCR和多重PCR测量mtDNA拷贝数和mtDNA缺失水平。
NAFLD患者的mtDNA拷贝数相对表达比健康对照高3.7倍（P<0.0001）。在调整年龄、BMI和性别后，结果仍然显著（P=0.02）。此外，非酒精性脂肪肝（NAFL）和非酒精性脂肪性肝炎（NASH）患者mtDNA拷贝数分别比健康对照高4.3倍（P<0.0001）和3.2倍（P<0.0001）。最后，结果显示，在20例对照受试者的任何肝组织样本中均未检测到4977bp缺失，而43例NAFLD患者中有8例（18.6%）在其肝组织中显示出4977bp缺失（P=0.039）。
本研究表明肝组织中的mtDNA含量与NAFLD易感性之间存在关联，这可能是对累积氧化损伤暴露的代偿反应的结果。
