The Genetics of Alcohol Metabolism: Role of Alcohol Dehydrogenase and Aldehyde Dehydrogenase Variants
By H. Edenberg. Alcohol Research and Health, 2007
826 citations recorded by the source corpus.
The primary enzymes involved in alcohol metabolism are alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). Both enzymes occur in several forms that are encoded by different genes; moreover, there are variants (i.e., alleles) of some of these genes that encode enzymes with different characteristics and which have different ethnic distributions. Which ADH or ALDH alleles a person carries influence his or her level of alcohol consumption and risk of alcoholism. Researchers to date primarily have studied coding variants in the ADH1B, ADH1C, and ALDH2 genes that are associated with altered kinetic properties of the resulting enzymes. For example, certain ADH1B and ADH1C alleles encode particularly active ADH enzymes, resulting in more rapid conversion of alcohol (i.e., ethanol) to acetaldehyde; these alleles have a protective effect on the risk of alcoholism. A variant of the ALDH2 gene encodes an essentially inactive ALDH enzyme, resulting in acetaldehyde accumulation and a protective effect. It is becoming clear that noncoding variants in both ADH and ALDH genes also may influence alcohol metabolism and, consequently, alcoholism risk; the specific nature and effects of these variants still need further study.
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Citations in the corpus
- Australian Dietary Guidelines (2006, background): “It takes approximately one hour for the liver to clear the alcohol from one standard drink from the body, although this time varies depending upon liver size, lean body mass, individual alcohol tolerance and genes controlling the expression of alcoholmetabolising enzymes in the liver [660-662].”
- The Role of Early Life Stress as a Predictor for Alcohol and Drug Dependence (2010, background): “Another important risk-reduction factor is the inability to tolerate the aversive effects of alcohol, specifically the “flushing response”, as is the case in 50% of South East Asians who have genetic variants that result in absent or inefficient alcohol-metabolizing enzymes (Edenberg 2007).”
- Strong Protective Effect of The Aldehyde Dehydrogenase Gene (ALDH2) 504lys (*2) Allele Against Alcoholism And Alcohol-Induced Medical Diseases in Asians (2011, background): “The other genes are in black zygous and 504lys/504lys homozygous has almost no detectable ALDH2 activity in the liver (Edenberg 2007).”