Genes May Play an Important Role in Alcohol Dependency

A gene that regulates how quickly the body metabolizes alcohol plays a significant role in risk for alcohol dependence, a new study says.
It’s not the only factor in alcoholism risk. Culture, environment, and other genes also play a part, experts say.
However, the findings could help develop new treatments for the disease.
“We are influenced by nature, nurture, and what I call neighborhood, or the community that surrounds you,” Dr. Michael Genovese, chief medical officer of addiction and mental health treatment provider Acadia Healthcare, told Healthline. “People can have a genetic susceptibility to alcohol dependence, which often coincides with susceptibility to other mental health conditions.”
“At the same time,” he added, “repeated exposure to alcohol consumption and abuse can impact drinking behaviors later in life. Continued genetic research is critical as it can eliminate guesswork and help with the identification, prevention, and individualized treatment of substance use disorder.”
In the study, researchers in the Substance Use Disorders working group of the Psychiatric Genomics Consortium compared the genomes of 15,000 people diagnosed with alcohol dependence with that of 38,000 people who were not alcohol dependent.
They found that those who carried the ADH1B variant of the alcohol dehydrogenase (ADH) gene, which regulates how the body converts alcohol to a substance called acetaldehyde, were more likely to become alcohol dependent than those who lacked this variant of the gene.
ADH1B significantly reduces the clearance rate of alcohol from the liver.
But people with ADH1B*2, another variant of the ADH gene, rapidly process alcohol, quickly elevating levels of acetaldehyde, the alcohol metabolite that causes hangovers.Genetics and alcohol dependence
Gene variants ALDH1A1*2 and ALDH1A1*3, often found in African-Americans, also have been associated with a high risk of alcoholism, according to psychiatrist and addiction medicine expert Dr. Indra Cidambi, founder of the Center for Network Therapy.
On the other hand, previous studies have shown that people with the ADH1B*2 gene variant — including many individuals of Asian descent — are at reduced risk of alcohol dependence, probably because of the unpleasant effects of acetaldehyde associated with drinking.
The new study included genetic data from people of European and African ancestry. The same ADH1B gene was linked to alcoholism risk in both populations but in different variants.
“Genetic differences in these enzymes explains why certain ethnic groups have lower rates of alcohol-related problems,” Cidambi told Healthline.
Carriers of ADH1B experience fewer adverse side effects when drinking due to their slower alcohol metabolism, which could explain their elevated risk.
“The strong ‘Asian flushing’ response, which includes rapid heartbeat, nausea, and other unpleasant feelings, tends to decrease drinking,” Arpana Agrawal, PhD, a researcher at Washington University School of Medicine in St. Louis, told Healthline.
“The biggest contributor to that reaction is a variant in aldehyde dehydrogenase 2 (ALDH2) that greatly slows the removal of the aversive acetaldehyde. Many individuals in Asian populations have that variant, as well as one of the protective variants in ADH1B that speeds the processing of alcohol. These variants in alcohol metabolism have the strongest, best-documented impact on risk for alcoholism.”
Implications for treatment
Disulfiram (Antabuse), the first drug approved by the U.S. Food and Drug Administration (FDA) to treat alcohol dependence, works by disrupting the metabolism of acetaldehyde into harmless acetic acid.
This disruption causes a range of unpleasant side effects when alcohol is consumed.
Genes may also play a role in the effectiveness of the drug naltrexone, used to prevent relapse to drinking among people who misuse alcohol.

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