A rare nicotine-receptor gene variant makes it easier for carriers to avoid heavy smoking

An international team of geneticists — including researchers from Mexico — found that people who carry a rare variant of a nicotine receptor gene are less likely to develop nicotine dependence. The findings could eventually help scientists develop medications to treat nicotine addiction.
Researchers from the United States, the United Kingdom, and Mexico sequenced the genomes of 37,897 avid smokers who participated in a long-term health study in Mexico City.
The team identified the p.Glu284Gly variant of the CHRNB3 gene, which encodes the β3 subunit of the nicotinic acetylcholine receptor, as reported by the study’s lead authors, Veera Rajagopal and Giovanni Coppola from the Regeneron Genetics Center, to IFLScience. This variant was more prevalent among members of the indigenous Mexican population.
Researchers found that carriers of one or two copies of the p.Glu284Gly variant smoked significantly less than non-carriers. Those with one copy smoked, on average, 21 percent fewer cigarettes, while those with two copies smoked 78 percent fewer cigarettes.
By comparing these findings with results from European and Asian cohorts drawn from British and Japanese biobanks, scientists observed similar effects associated with variants of the CHRNB3 gene. This suggests that these variants may reduce smoking across different populations, though the authors emphasized that larger studies are needed to confirm the result.

According to Rajagopal and Coppola, this represents “a striking, incredible strength and consistency of the signal across three completely independent populations.”
“The variant found in indigenous Mexicans, the variant found in East Asian populations, and the combined European signal are different mutations in the same gene, yet they produce nearly identical effects. Such interethnic convergence in genetics is relatively rare,” the scientists explained.
These results suggest that for many people, how much they smoke is driven less by willpower and more by biology. “Some people are indeed wired differently, and understanding these traits is the first step toward developing more effective tools to help them,” the researchers said.
The study’s findings were published in the journal Nature Communications.
According to the World Health Organization, smoking tobacco cigarettes is responsible for over 7 million deaths each year. This figure includes about 1.6 million non-smokers who die from the effects of secondhand smoke. It remains a significant public health issue worldwide. However, there has been little progress in developing medications that could assist those suffering from nicotine addiction.