Genetic Polymorphisms of and in Alcohol-Induced Liver Injury: Molecular Mechanisms of Inflammation and Disease Progression in East Asian Populations.

Alcohol-associated liver disease (ALD) is a major cause of liver-related mortality worldwide; however, only a subset of heavy drinkers develop progressive disease, suggesting a role for host genetics. In East Asian populations, functional polymorphisms in alcohol-metabolizing enzymes, such as alcohol dehydrogenase 1B (ADH1B) and aldehyde dehydrogenase 2 (ALDH2), are common and significantly affect acetaldehyde metabolism. ADH1B accelerates ethanol oxidation, whereas ALDH2 impairs acetaldehyde detoxification and increases oxidative stress, inflammation, and liver injury. Based on genotype combinations, individuals were stratified into five alcohol sensitivity groups with differing risks of cirrhosis and cancer. Although ALDH2 deficiency often suppresses alcohol intake via aversive reactions, paradoxically, continued drinking increases the risk of liver and gastrointestinal cancers. Genetic risk stratification may inform personalized prevention and precision of public health approaches. However, expansion of direct-to-consumer genetic testing has raised ethical and educational challenges. Understanding the interaction between alcohol metabolism and genetic variations is crucial for identifying high-risk individuals and guiding tailored interventions in East Asian populations.