Polymorphisms in the genes encoding for the alcohol-metabolizing enzymes such as the alcohol dehydrogenase IB (ADH1B) and aldehyde dehydrogenase 2 (ALDH2) influence alcohol consumption and risk of alcohol use disorders. ADH1B and ALDH2 catalyze consecutive steps in alcohol metabolism. In adults, these enzymes play an important role although several other enzymes also catalyze these metabolic steps, including catalase, cytochrome P450, and other enzymes in the ADH and ALDH gene families. ADH oxidizes ethanol to acetaldehyde, which is then converted to acetate by ALDH. Acetaldehyde is toxic and adducts with both proteins and DNA. Both acetaldehyde and alcohol are recognized as mutagens. Acetaldehyde is a potent releaser of histamine, and thereby triggers flushing, an aversive reaction characterized by headache, nausea, palpitations, and flushing of the skin. Ordinarily, acetaldehyde is rapidly converted to acetate, and levels of acetaldehyde are very low even after alcohol ingestion. However, if aldehyde dehydrogenase is blocked by disulfiram (a medication used to help alcoholics maintain abstinence) then flushing is observed after ingestion of small quantities of alcohol. The acetaldehyde accumulation can lead to increased risk of upper
