Smoking Addiction: Genetic Insights and Quitting Strategies

Scientists have recently discovered hundreds of genetic variations that are thought to affect a wide range of factors, including when individuals try smoking, how wonderful that first cigarette feels, how often they light up, and how difficult it is to stop. Certain variations impact the rate at which we metabolize nicotine, while others determine our level of sensitivity to it. However, little is known about how they interact with other genetic variations and with one another.

A recent study from the University of Colorado Boulder provides unprecedented light on these interactions and fresh information on the most well-known smoking-related variation to date—nicknamed “Mr. Big”.

“We know that smoking is highly heritable, with genetic differences accounting for 40% to 75% of the differences in people’s smoking behaviors,” said Pamela Romero Villela, a Ph.D. student in the Department of Psychology and Neuroscience and first author of the study in the journal Drug and Alcohol Dependence. “The more we can understand what those genes do and how they interact, the better equipped we will be to develop personalized approaches to helping people quit.”

Besides Mr. Big

In the United States, smoking is associated with one in five fatalities, while 22% of persons globally use nicotine.

Romero Villela worked on the study alongside Marissa Ehringer, a professor of integrative physiology with more than 20 years of experience studying substance use problems.

They focused on the genetic variant known as “Mr. Big,” or single nucleotide polymorphism (SNP), rs16969968 since it has been the most often duplicated genetic variable linked to smoking habits.

Mr. Big affects the degree to which nicotine binds to brain receptors and is encoded by the CHRNA5F gene (nicotinic acetylcholine receptor 5). It has been demonstrated that those who have the AA version of Mr. Big smoke more and are less sensitive to nicotine. 

“It kind of numbs your response so for you to feel the same effect as someone who smoked one cigarette you might have to smoke almost one and a half cigarettes,” said Romero Villela. 

Their research indicates that this is not the end of the narrative.

A customized strategy

The scientists found genes and variations related to smoking addiction in a completely separate part of the genome that appears to interact with Mr. Big in a way that alters smoking habits when they analyzed the genetic data from around 165,000 smokers of European, South Asian, and Finnish heritage, who were current or past smokers.

Interestingly, smokers who carried both the rs73586411 genetic mutation and the risk-boosting form of Mr. Big smoked far less than predicted.

“We basically found another variant that ameliorates the effect of Mr. Big,” said Romero Villela.

To fully comprehend the functions of the genes mentioned in the paper, more investigation is required. It’s interesting to note that TMEM230 has been linked to Parkinson’s disease in the past. Certain illness symptoms have been shown to be mitigated by nicotine.

The authors of the study envision a time when individuals may receive a “polygenic risk score” that takes into account their interactions and gene variations to offer individualized quitting advice. For example, early research has previously indicated that individuals with high-risk genotypes in the CHRNA5 area could benefit more from nicotinic receptor-targeting drugs. 

In time, scientists may be able to create drugs that replicate the way a variation lessens the desire to smoke if they can figure out what it does.

“Genes don’t operate in a vacuum,” said Ehringer. “If our ultimate goal is more personalized medicine, we have to understand these interactions better.”

For more Information: Loci on chromosome 20 interact with rs16969968 to influence cigarettes per day in European ancestry individuals, Drug and Alcohol Dependence, https://www.sciencedirect.com/science/article/abs/pii/S0376871624000474?via%3Dihub