Genetic Predisposition to MASLD: Potential for Therapeutic Management

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is now the most common liver disease worldwide, with a continuously increasing prevalence. The mechanisms involved in its pathophysiology are numerous and may include metabolic, environmental, and genetic factors. Genome-wide association studies have identified key genetic variants, most notably in PNPLA3, TM6SF2, MBOAT7, GCKR, and HSD17B13. This mini review discusses the mechanisms through which these variants contribute to the disease pathogenesis, an area that remains a rapidly evolving field of research. Beyond improving our understanding of MASLD, the identification of these variants may also aid in the development of targeted pharmacological approaches. We first summarize the major genetic variants associated with MASLD and then present findings from studies exploring how these variants may influence the efficacy of emerging pharmacotherapies. Finally, we examine the therapeutic agents in the field of precision medicine that are currently being tested in clinical trials. These therapeutic opportunities are a promising approach that may provide individualized solutions for this chronic liver disorder that affects a wide range of the population.