title: Liver Mitochondrial DNA Copy Number and Deletion Levels May Contribute to Nonalcoholic Fatty Liver Disease Susceptibility.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Sharareh
authors.initials: S
authors.lastname: Kamfar
authors.affiliation: 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.
authors.forename: Seyed Moayed
authors.initials: SM
authors.lastname: Alavian
authors.affiliation: Department of Medical Genetics, National Institute for Genetic Engineering and Biotechnology, Tehran, IR Iran.
authors.forename: Massoud
authors.initials: M
authors.lastname: Houshmand
authors.affiliation: Shohada Hospital of Harsin, Kermanshah University of Medical Sciences, Kermanshah, IR Iran.
authors.forename: Reza
authors.initials: R
authors.lastname: Yadegarazari
authors.affiliation: School of Medicine, Shahid Beheshti Hospital, Hamadan University of Medical Sciences, Hamadan, IR Iran.
authors.forename: Bahram
authors.initials: B
authors.lastname: Seifi Zarei
authors.affiliation: Obesity Treatment Center, Department of Surgery, Shahed University, Tehran, IR Iran.
authors.forename: Alireza
authors.initials: A
authors.lastname: Khalaj
authors.affiliation: Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, IR Iran.
authors.forename: Noshin
authors.initials: N
authors.lastname: Shabab
authors.affiliation: 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.
authors.forename: Massoud
authors.initials: M
authors.lastname: Saidijam
keywords: Copy Number Variations; Mitochondrial DNA; Non-Alcoholic Fatty Liver Disease; Nonalcoholic Steatohepatitis