Genetic predeterminants and recent advancements in steatotic liver disease: A roadmap toward precision hepatology

Figure 1 Global prevalence of metabolic dysfunction-associated steatotic liver disease, based on the systematic review and meta-analysis by Younossi et al[14]. The map displays regional variation in metabolic dysfunction-associated steatotic liver disease prevalence, with the highest rates observed in Latin America (44.37%) and the Middle East and North Africa (MENA; 36.5%), followed by Southeast Asia (33.07%), North America (31.2%), and Australia (31.2%). Western Europe and East Asia show lower rates at 25.1% and 29.71%, respectively. These differences likely reflect a combination of genetic predisposition (e.g., PNPLA3 and TM6SF2 allele frequencies), dietary patterns, urbanization, and metabolic comorbidities[14].

Figure 2 Schematic representation of intracellular pathways highlighting the key genes PNPLA3, TM6SF2, GCKR, and GCKR involved in susceptibility to metabolic dysfunction-associated steatotic liver disease development. The schematic highlights how variants in PNPLA3 (rs738409), TM6SF2 (rs58542926), GCKR (rs641738C>T), and GCKR (rs1260326) disrupt lipid metabolism in hepatocytes. PNPLA3 impairs triglyceride hydrolysis, TM6SF2 impairs very low-density lipoprotein secretion, GCKR impairs phospholipid metabolism, while GCKR increases glucose uptake and lipogenesis. This figure was created by BioRender.com (Supplementary material).