Shahed University
Liver Mitochondrial DNA Copy Number and Deletion Levels May Contribute to Nonalcoholic Fatty Liver Disease Susceptibility
Alireza Khlaj | Sharareh Kamfar | Seyed Moayed Alavian | Massoud Houshmand | Reza Yadegarazari | Bahram Seifi Zarei | Noshin Shabab | Massoud Saidijam
URL :
http://research.shahed.ac.ir/WSR/WebPages/Report/PaperView.aspx?PaperID=137951
Date :
2016/11/09
Publish in :
Hepatitis Monthly
DOI :
https://doi.org/10.5812/hepatmon.40774
Link :
http://dx.doi.org/10.5812/hepatmon.40774
Keywords :
Non-AlcoholicFattyLiverDisease,NonalcoholicSteatohepatitis,MitochondrialDNA,CopyNumberVariations
Abstract :
Background: There is growing evidence that deficiencies observed in the mitochondrial DNA (mtDNA) functions could play an importantroleinthepathogenesisof non-alcoholicfattyliverdisease(NAFLD).WehypothesizedthatgeneticvariationsinmtDNA couldaffectthemitochondrialfunctionandcontributetotheNAFLDsusceptibility. Objectives:Inthisstudy,thepossibleassociationofthemtDNAcopynumberand4,977-bpdeletionlevelswithNAFLDsusceptibility inasampleof Iranianpopulationwasevaluated. Methods:Thiscase-controlstudyincluded43NAFLDpatientsand20controlsubjects. GenomicDNAwasextractedfromfreshliver tissue samples by using a DNA isolation kit. The mtDNA copy number and mtDNA deletion levels were measured by quantitative real-timePCRandmultiplexPCR. Results: Therelativeexpressionof mtDNAcopynumberwas3.7foldhigherinNAFLDpatientsthanhealthycontrols(P 0.0001). Theresultsremainedsignificantafteradjustmentforage,BMI,andgender(P=0.02). Inaddition,themtDNAcopynumberwas4.3 (P 0.0001) and 3.2-fold (P 0.0001) higher in nonalcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH) patients thanhealthycontrols,respectively.Finally,theresultsshowedthatthe4,977-bpdeletionisnotdetectedinanyoflivertissuesamples obtainedfromthe20controlsubjectswhereas8outof 43NAFLDpatients(18.6)showedthe4,977-bpdeletionintheirlivertissues (P=0.039). Conclusions: ThisstudyindicatedanassociationbetweenmtDNAcontentinthelivertissueandNAFLDsusceptibilitythatmaybe aconsequenceof compensatoryresponsetothecumulativeexposurestooxidativedamage
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Alireza Khlaj