were based on candidate genes. The main pathway of ethanol metabolism involves its conversion to acetaldehyde by alcohol dehydrogenase (ADH; Figure 1). Acetaldehyde is oxidized to acetate by aldehyde dehydrogenase (ALDH). The activated form of acetate, acetyl-CoA, can be metabolized into ketone bodies, fatty acids, amino acids and steroids, in addition to oxidation in the Krebs cycle. Cytochrome P450s (for example, those encoded by the gene CYP2E1) and catalase also metabolize a small fraction of ingested ethanol. Multiple ADH and ALDH enzymes are encoded by different genes [7], and different ADH and ALDH alleles can differ in expression levels and in the rate at which their corresponding enzymes metabolize ethanol or acetaldehyde. The ADH1B His48Arg and ALDH2 Lys487 polymorphisms have long been associated with risk of alcoholism, and directly and predictably lead to alcohol-induced flushing through molecular mechanisms that include accumulation of acetaldehyde and release of histamine [8]. ADH1B, ALDH2 and ADH4 influence alcohol consumption and have been implicated as risk factors for developing alcohol abuse or dependence [9-11].
