ADH1B (alcohol dehydrogenase 1B) encodes a key enzyme involved in alcohol metabolism that catalyzes the NAD-dependent oxidation of ethanol to acetaldehyde 1. The enzyme also participates in retinoid metabolism by catalyzing the oxidation of all-trans-retinol and related derivatives 2. Mechanistically, ADH1B variants, particularly the Arg48His polymorphism (rs1229984), significantly affect enzyme activity and alcohol metabolism rates 1. Individuals carrying certain ADH1B alleles produce more active enzymes, resulting in rapid ethanol conversion to acetaldehyde, which creates an aversive reaction that protects against alcohol dependence 3. Disease relevance is substantial, as meta-analysis of over 19,000 subjects demonstrated strong associations between ADH1B variants and alcohol dependence (OR 2.06), with particularly robust effects in Asian populations 4. The gene shows complex tissue-specific expression patterns that may influence cardiac and metabolic traits beyond alcohol metabolism 2. Clinical significance extends to multiple diseases, with genetic studies linking ADH1B to gout, liver cirrhosis, stroke, and various cancers 56. Evolutionary evidence suggests ADH1B underwent natural selection for functions beyond alcohol metabolism, supporting its broader physiological importance 2.