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Researchers find new genetic influences on alcohol metabolism

Alcohol's effects on behavior are related to how much alcohol reaches a person's brain. How much alcohol an individual has in his or her brain after drinking is related to his or her metabolism of alcohol. In other words, two people may drink the same amount of alcohol, but differences in their metabolism could make one individual more intoxicated than the other. A study in the May issue of Alcoholism: Clinical & Experimental Research looks for additional genes that may influence alcohol metabolism.

"Although genetic factors are known to influence individual differences in alcohol metabolism," said John Crabbe, director of the Portland Alcohol Center and corresponding author for the study, "most of that knowledge is limited to alcohol or aldehyde dehydrogenases. This study used a mouse model to look for the locations of additional genes affecting alcohol metabolism. By studying many genetically different mouse strains, we found evidence for several genes that significantly affect how much alcohol reaches the brain, and how long it remains there. Our findings tell us approximately where in the genome of the mouse those genes are, for example, on which ends of which chromosomes, in this case chromosome 17. However, we have only a 'neighborhood' address now, and each neighborhood houses many specific genes. So, we need further studies to pinpoint which genes are actually responsible."

Alcohol is metabolized by the enzyme alcohol dehydrogenase to acetaldehyde. Acetaldehyde is a lot like formaldehyde, the chemical used to "pickle" organs for long-term storage; it is toxic, and when an individual has high acetaldehyde levels, they feel nauseated, flushed, hot, and dizzy. Fortunately, acetaldehyde is quickly converted into acetate and carbon dioxide by the enzyme aldehyde dehydrogenase (ALDH). However, if ALDH isn't doing its job efficiently, an individual who drinks alcohol will accumulate acetaldehyde in his or her blood and brain.
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