Mitochondrial Genome Variation and Its Association with Non-Alcoholic Fatty Liver Disease in Patients from South East Nigeria

Non-alcoholic fatty liver disease (NAFLD) is a rising non-communicable disease in Nigeria driven by urbanisation, dietary transition, and genetic susceptibility. Mitochondrial dysfunction is a recognised pathophysiological mechanism in NAFLD, and mitochondrial genome (mitogenome) variation may influence individual susceptibility. This study investigated mitogenome variation and its association with NAFLD in patients from South East Nigeria. One hundred and twenty NAFLD patients diagnosed by ultrasound and liver enzymes at three tertiary hospitals in Enugu, Anambra, and Imo States were compared with 120 healthy controls matched for age and sex. Complete mitogenome sequencing was performed using Sanger sequencing of amplified mitochondrial segments. Haplogroup assignment was performed using HaploGrep2, and heteroplasmy levels were assessed. POLG gene nuclear variants were also genotyped as a complementary mitochondria-related analysis. Haplogroup L3 was the most frequent haplogroup in both groups. However, specific mitogenome haplogroups and heteroplasmy at complex I genes showed suggestive associations with NAFLD status. Elevated heteroplasmy in NADH dehydrogenase subunit genes correlated with higher hepatic enzyme levels. These findings suggest mitochondrial genome variation as a contributing genetic factor in NAFLD susceptibility in South East Nigerian populations. Keywords: mitochondrial genome, NAFLD, heteroplasmy, haplogroup, South East Nigeria