Mitochondrial Epigenetics Modulates The Histological Disease Severity of Nonalcoholic Fatty Liver Disease

PIROLA C; FERNADEZ GIANNOTTI T; BURGUEÑO A,; CASTANO G; SOOKOIAN S

BOSTON

Congreso; 63rd Annual Meeting American Association for the Study of Liver Diseases; 2012

AASLD

Nonalcoholic fatty liver disease (NAFLD) is a clinical condition that refers to progressive histological changes ranging from simple steatosis (SS) to nonalcoholic steatohepatitis (NASH). The evidence strongly suggests that mitochondrial dysfunction might be the bifurcation point in the pathogenesis of NAFLD progression. The presence of cytosine at the carbon-5 position (5mC), in CpG dinucleotides in human mitochondrial DNA (mtDNA) is a novel finding recently reported that lead to us to question whether this epigenetic modification might play a role in the molecular changes that mediate the transition from SS to NASH. Hence, we evaluated the status of 5mC of liver mtDNA in selected regions of the mtDNA genome, such as D-loop control region, and mitochondrially encoded NADH dehydrogenase 6 (MT-ND6) and cytochrome C oxidase I (MT-CO1) in liver biopsies obtained from patients with NAFLD in a case-control design; 45 patients and 18 controls were evaluated. Results: MT-ND6 methylation was higher in the liver of NASH than SS patients (p