The latest critique from the ISFAR considers a study that looks at the effects of genetic factors on the metabolism of alcohol

The latest critique from the ISFAR considers a study that looks at the effects of genetic factors on the metabolism of alcohol

A recent paper by Israel Y et, published in Front Behav Neurosci, presents an excellent summary of the effects of genetically-determined enzymes that affect the metabolism of alcohol; such factors relate strongly to both the rewarding and the aversive effects of alcohol.

Of almost 100 genes that have been found to relate to alcohol metabolism, the two major ones appear to be alcohol dehydrogenase and aldehyde dehydrogenase. The authors describe the metabolism of alcohol into acetaldehyde (toxic) by alcohol dehydrogenase, and then focus especially on the metabolism of acetaldehyde by aldehyde dehydrogenase-2 into acetate (harmless). 

Previous studies have shown that 20% to 40% of individuals of East Asian origin have a point mutation in the genes that code for high-affinity aldehyde dehydrogenase-2; such people tend to show high levels of acetaldehyde and develop flushing, tachycardia, headache, nausea, and emesis from even small amounts of alcohol. Being very intolerant of alcohol, they are at very low risk of alcohol abuse. This mutation is much less common among European and North American populations.

The authors' study focuses on genetically-determined mechanisms related to the metabolism of alcohol and acetaldehyde, and describes numerous ways that the metabolism, especially of acetaldehyde, may be modified, both in the periphery of the body and in the brain. Individuals with a mutation of the aldehyde dehydrogenase gene (the ALDH2*2 allele), and certain other genetically-determined enzymes, do not tolerate alcohol and are much less likely to become alcohol abusers.

The authors also describe what is known as the “alcohol deprivation effect”, in which animals given alcohol over a period of time, then deprived of alcohol, tend to drink excessively when alcohol is reintroduced. Drugs given to inhibit catalase activity block the excessive drinking when alcohol is reintroduced. The authors state that this suggests possible therapeutic avenues in the treatment of alcoholism, although extensive further research is needed. 

As pointed out by forum reviewers Van Velden and Kotze: “Alcoholism is a huge problem worldwide, and we need to understand this addiction better if we want to combat this negative effect of alcohol consumption in humans. Alcohol use disorders (AUD) involving hazardous, harmful and addictive misuse of alcohol are widespread in most parts of the world. This paper highlights the molecular understanding of alcoholism, and may contribute to the therapeutic armamentarium of the physician in treating and preventing alcoholism.

“This paper summarises research indicating that individuals carrying the ALDH2*2 allele are protected between 66% (heterozygous ALDH2*1/ALDH2*2) and 99% (homozygous ALDH2*2/ ALDH2*2) against alcoholism. These studies indicate that humans carrying the ADH1B*2 (ADH-47His) gene are protected against alcoholism. These studies strongly suggest possible therapeutic avenues in the treatment of alcoholism. The paper contributes to a better understanding of the genetic polymorphisms leading to alcohol abuse, and this can be of great value.”

To read the full critique, click here.

These critiques are released with the permission of ISFAR.