A genetic variant that causes an ‘alcohol flush’ response increases the risk of heart disease, especially in drinkers, by causing inflammation in blood vessels
health
January 25, 2023
People with the ALDH2*2 gene variant have difficulty metabolizing alcohol Shutterstock/Fenea Silviu
About 8% of the world’s population carries a genetic mutation called ALDH2*2 It impairs the body’s ability to metabolize alcohol, causing unpleasant symptoms such as flushing soon after drinking. Researchers are now showing why this mutation increases the risk of heart disease.
“We are trying to understand why ALDH2*2 It’s associated with a higher risk of coronary artery disease at the cellular level,” said Hongchao Guo of Stanford University in California.
of ALDH2 This gene encodes a version of the enzyme alcohol dehydrogenase that breaks down the toxic acetaldehyde produced when alcohol is metabolized and clears out other harmful substances known as free radicals.
of ALDH2*2 Mutations stop the enzyme from working. People with this mutation are at increased risk of many diseases, including heart disease, diabetes, and various cancers. It is not clear why this variant increases the risk of heart disease.
Guo and his colleagues first analyzed data from Japanese and British biobanks. They found that the risk of heart disease was four times higher in regular drinkers. ALDH2*2.
The volunteers’ ability to dilate blood vessels was then measured using a device called the EndoPAT.in people with ALDH2 In genes, this measure increases after drinking, ALDH2*2,fall. This may seem strange. ALDH2*2 They flush when they drink, but the flush is caused by the release of histamine, says Joseph Wu, a member of the Stanford team.
Then they created human stem cells ALDH2*2 Variants, and endothelial cells derived from them – types of cells that line blood vessels. They are, ALDH2*2 The cells had higher levels of free radicals and inflammation than normal endothelial cells, and were also unable to produce nitric oxide, which helps relax blood vessels. exacerbated by exposure.
Gene variants also impair new blood vessel growth. “This means that if a heart attack occurs, carriers have a lower ability to generate new blood vessels if they need to grow,” Guo says.
The team found that an existing diabetes drug called empagliflozin may reduce these harmful effects. ALDH2*2 People who often drink alcohol. But the takeaway message is clear for Wu. “If you’re deficient in this enzyme, don’t drink it,” he says.
Given its many negative consequences, there is debate as to why this mutation became widespread and common, and today it is found in more than a third of people from East Asia.
“My only explanation is that a lack of this enzyme makes you drink less and is less likely to become an alcoholic,” says Wu.
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