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UW-Madison study links nicotine addiction to genetic variation in brain
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UW-Madison study links nicotine addiction to genetic variation in brain

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Genetic variation in an enzyme that breaks down nicotine in the brain might help explain why some smokers become more addicted than others, UW-Madison researchers found.

Some smokers have more of an urge to light up right after they wake up, and UW-Madison researchers have identified a reason: genetic variation in a substance that breaks down nicotine in the brain.

The finding, by scientists at UW-Madison and Washington University in St. Louis, adds to growing research on genetic links to how much people smoke, how hard it is for them to quit and how likely they are to develop lung cancer.

Most of the attention has focused on genetic variation in enzymes that metabolize nicotine in the liver. Some studies suggest that dozens of genes could influence how addicted people become to smoking.

The new understanding about FMO3, an enzyme that metabolizes nicotine in the brain, could someday allow researchers to tailor tobacco cessation treatments to individual patients or develop new drugs to target the enzyme.

“The research clearly suggests that it’s not just one or two big players here, but that a lot of genes may contribute to these outcomes,” said Tim Baker, director of research at UW-Madison’s Center for Tobacco Research and Intervention.

Despite a steady decline in smoking in recent years, tobacco remains the leading cause of preventable death, according to the Centers for Disease Control and Prevention.

About 17.3 percent of Wisconsin adults smoked in 2015. That’s down from 20.9 percent in 2011. Still, nearly 800,000 adults and adolescents in the state continue to light up, resulting in about 7,700 deaths a year, according to the state Department of Health Services.

Nationally, 17.5 percent of adults smoked in 2015, and smoking causes 480,000 deaths a year, the CDC says. More than half of American smokers attempt to quit each year, but only 6 percent succeed.

The brain enzyme study, published earlier this year in The Pharmacogenomics Journal, involved 1,558 smokers, most of them in a study at UW-Madison of people who were trying to quit.

Smokers with genes that produce more FMO3, causing nicotine to be broken down more quickly in the brain, were more likely to say they smoke first thing in the morning — a key indicator of nicotine dependence.

“Even if they have a home smoking ban, they will go out into their porch or to the garage to have their cigarette right away, as soon as they get up,” Baker said.

Smokers with certain genetic types of the liver enzymes respond better to nicotine replacement therapy, researchers have found. It’s too early to tell if the same might be true for the brain enzyme.

The genetic information could eventually help more smokers quit, but Baker said they shouldn’t wait.

“Regardless of their genetic status, although some people are at greater risk than others, any kind of smoking is dangerous and they should do whatever they can to quit now,” he said.


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