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OBJECTIVE 45 patients and 18 near-normal liver-histology subjects. RESULTS: MT-ND6 methylation was higher in the liver of NASH than SS patients (p < 0.04) and MT-ND6 methylated DNA/unmethylated DNA ratio was significantly associated with NAFLD activity score (p < 0.02). Liver MT-ND6 mRNA expression was significantly decreased in NASH patients (0.26 ± 0.30) versus SS (0.74 ± 0.48), p < 0.003, and the protein level was also diminished. The status of liver MT-ND6 methylation in NASH group was inversely correlated with the level of regular physical activity (R = -0.54, p < 0.02). Hepatic methylation levels of D-Loop and MT-CO1 were not associated with the disease severity. DNA (cytosine-5) methyltransferase 1 was significantly upregulated in NASH patients (p < 0.002). Ultrastructural evaluation showed that NASH is associated with mitochondrial defects and peroxisome proliferation. CONCLUSION: Hepatic methylation and transcriptional activity of the MT-ND6 are associated with the histological severity of NAFLD. Epigenetic changes of mtDNA are potentially reversible by interventional programs, as physical activity could modulate the methylation status of MT-ND6.
Pirola et al. (Thu,) studied this question.