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Did you know DNA influences your response to alcohol?

Genetic variation determines how efficiently you are able to metabolize alcohol

Albert and his best friend Warren arrive at their first college party, excited and ready to celebrate the next chapter of their lives; college, new city and new friends. They grab a drink and head into the already crowded room. Ten minutes after finishing his first drink, Albert feels sweaty and flushed. By 10pm, just two hours and three drinks later, Albert is frantically looking for Warren. Now he’s sure something is wrong. He’s itchy all over his face, arms and back. A very worried Warren calls 9-1-1. This was the day Albert discovered he suffers from alcohol flush. Alcohol flush is one symptom of alcohol intolerance, when the body can’t break down alcohol properly. Other symptoms include nausea, dizziness, headaches, increased heart rate, insomnia and severe hangovers. Unfortunately, or fortunately, depending on how you feel about social drinking, alcohol intolerance is inherited.

Anyone who has had a drink knows the buzz usually wears off, as the body breaks down the alcohol. There are many different ways to clear alcohol, however most of it is metabolized in a two-step process involving two enzymes, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). ADH converts ethanol to acetaldehyde, which is then converted into acetate by ALDH. Acetate is similar to vinegar and is harmless, but acetaldehyde is toxic. The buildup of acetaldehyde, which is normally short-lived, is responsible for all of the symptoms associated with alcohol intolerance.

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People with alcohol intolerance carry genetic variants in genes that give instructions to make ADH and ALDH. Genetic variants are different versions of the same gene, due to small changes in the DNA. Variants in two genes (ADH1B and ADH1C) encoding ADH enzymes, cause a faster than normal conversion of ethanol to acetaldehyde (first step of alcohol metabolism), resulting in elevated acetaldehyde before it can be cleared in the second step of alcohol metabolism. In contrast, a variation in the ALDH2 gene, results in an enzyme with reduced activity, so the second step of alcohol metabolism is slower than normal. But the consequences are the same – an accumulation of toxic acetaldehyde. Increased acetaldehyde levels are not only responsible for the short-term symptoms mentioned above, but can also cause long-term damage to brain cells. This leads to the symptoms typically associated with alcoholism, including memory loss, mental confusion, anxiety and depression. However, unlike the excessive alcohol consumption of alcoholics, genetically susceptible individuals can suffer from these same complications even if only a small quantity of alcohol is consumed.

Symptoms of alcohol intolerance vary from person to person because of how genes are passed on. We inherit two copies of each gene, one from our mother and one from our father. A person, who inherits two ‘defective’ versions of the ADH1B gene for example, will experience more severe symptoms compared to someone with only one ‘defective’ copy. However, because the symptoms are often not severe enough to stop them from drinking, people with only one ‘defective’ version are at higher risk for alcohol-related complications, like an increased risk of cancer and heart disease.

The ALDH2 variant responsible for the alcohol flush reaction is most commonly found in people of East Asian descent. While turning red or appearing intoxicated after just one drink may seem like a social faux pas, the flush response can signal risks associated with drinking. Studies show that if a person who experiences an alcohol flush reaction continues to drink, they increase their risk of esophageal cancer by 10-fold in the case of a moderate drinker or up to 90-fold for a heavy drinker. Alcohol ‘flushers’ who consume more than four drinks a week are also at higher risk for hypertension. Inheriting any of the genetic variants linked to alcohol intolerance also increases the risk for other cancers, cardiovascular issues and strokes.

If you have always wondered why a drink or two makes you uncomfortable, experienced severe hangovers from just one glass of wine or are a ‘flusher’, you may have alcohol intolerance. A simple genetic test can provide you with the answer. But how you let this information influence your social drinking is still entirely up to you.

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