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. Objectives: 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.