Genetic and epigenetic determinants of non-alcoholic fatty liver disease (NAFLD) in lean individuals: a systematic review

Abstract

Background Non-alcoholic fatty liver disease (NAFLD) is common in obese individuals, but its occurrence in lean individuals and the underlying mechanisms are not well understood. This study aimed to systematically review the literature on the genetic and epigenetic factors influencing NAFLD in lean individuals. Methods A comprehensive search was conducted on April 2 nd , 2023, in seven databases using specific criteria. Only peer-reviewed studies in English, focusing on genetic or epigenetic effects on NAFLD in lean individuals, were included for qualitative synthesis. The Newcastle Ottawa Scale (NOS) was used for quality assessment. This study is registered with PROSPERO (CRD42023413809). Results Following PRISMA guidelines, 18 studies were included in this review. The studies were conducted globally, with varying sample sizes and study designs. The NOS quality assessment revealed a moderate overall quality with variations in risk of bias and limitations in comparability and ascertainments of exposure among contributing studies. Genetic determinants related to lipid metabolism, inflammation, and oxidative stress pathways were identified, including PNPLA3 and TM6SF2 gene variants associated with increased NAFLD risk in lean individuals. Epigenetic modifications, particularly depletion of histone variants, were also implicated. However, some studies found no significant associations between genetic or clinical characteristics and lean NAFLD. Less frequent genetic risk factors, such as CETP and APOC3 gene variants, were reported. Conclusions This systematic review underscores the importance of investigating genetic and epigenetic factors in lean NAFLD. The findings highlight the role of PNPLA3 and TM6SF2 gene variants and suggest potential epigenetic contributions. Further research is needed to fully understand the genetic and epigenetic mechanisms underlying NAFLD in lean individuals.

Evolutive Models, Algorithms and Predictive Parameters for the Progression of Hepatic Steatosis

“…Genetic Biomarkers: Genetic variants associated with hepatic steatosis, such as PN-PLA3 and TM6SF2 polymorphisms, have been studied as predictors of disease progression [50]. Genetic biomarkers offer valuable information about the underlying genetic predisposition to hepatic steatosis progression.…”