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Genetic mutation may make it harder for some people to quit smoking

A genetic mutation that was already known to be involved in nicotine sensitivity may also play a role in relapses among smokers, according to a new study led by the Institut Pasteur.

Relapse is very common when people are trying to quit smoking, and nicotine dependence is the leading preventable cause of death in developed countries. Every year, seven million people die from tobacco use.

Tobacco addiction is caused by nicotine, which binds to the nicotinic receptors in the brain and activates the reward system.

Studies have demonstrated in recent years that a mutation in the CHRNA5 gene that codes for the α5 nicotinic receptor subunit is associated with a notable increase in the risk of nicotine dependence. The mutation is very common in the general population, and is carried by approximately 35 percent of Europeans and up to 50 percent of the Middle Eastern population.

In the current study, the experts wanted to understand the mechanism underlying this mutation and to determine what stage of nicotine dependence is influenced by it.

Using an advanced molecular genetics technique, the scientists introduced the mutation to a rat. They examined its effect on various behaviors associated with nicotine dependence and found that the rat consumed nicotine more frequently and in higher doses.

“This study enabled us to assess the impact of this mutation on various stages of nicotine dependence with a greater degree of accuracy,” said study lead author Benoit Forget. “It provided us with an initial explanation for its mechanism of action, which promotes relapse to nicotine-seeking behavior after smoking cessation.”

Study co-author Uwe Maskos added: “The results suggest that a drug capable of increasing the activity of nicotinic receptors containing the α5 subunit could reduce tobacco consumption and lower the risk of relapse after cessation.”

The study is published in the journal Current Biology.

By Chrissy Sexton, Staff Writer

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