liver mitochondrial dna copy number and deletion levels may contribute to nonalcoholic fatty liver disease susceptibility

Background: there is growing evidence that deficiencies observed in the mitochondrial dna (mtdna) functions could play an important role in the pathogenesis of nonalcoholic fatty liver disease (nafld). we hypothesized that genetic variations in mtdna could affect the mitochondrial function and contribute to the nafld susceptibility.objectivesin this study, the possible association of the mtdna copy number and 4,977bp deletion levels with nafld susceptibility in a sample of iranian population was evaluated.methodsthis casecontrol 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 realtime pcr and multiplex pcr.resultsthe 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 3.2fold (p < 0.0001) higher in nonalcoholic fatty liver (nafl) and nonalcoholic steatohepatitis (nash) patients than healthy controls, respectively. finally, the results showed that the 4,977bp 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).conclusionsthis 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.