Researchers have identified a rare genetic variant linked to reduced cigarette consumption, offering potential insights into nicotine addiction and novel therapeutic strategies. The variant, found in the CHRNB3 gene, which encodes a subunit of nicotinic acetylcholine receptors in the brain, appears to lessen the drive to smoke in individuals who carry it.
The discovery, published in Nature Communications, stems from an analysis of over 37,897 current smokers participating in the Mexico City Prospective Study. Individuals with one copy of the variant smoked approximately 21% fewer cigarettes daily compared to those with the common gene version, while those with two copies smoked roughly 78% fewer, according to the study.
The CHRNB3 gene plays a crucial role in mediating the effects of nicotine in the brain. Nicotinic acetylcholine receptors bind to nicotine, triggering neurological responses that contribute to addiction. Variants in other genes coding for these receptors, such as CHRNB2, have previously been associated with altered smoking behavior, suggesting a genetic component to nicotine dependence.
The newly identified variant was more prevalent among people of Indigenous Mexican ancestry. Still, researchers found similar effects involving variants in CHRNB3 in populations of European and East Asian descent, analyzing data from the UK Biobank (approximately 130,000 participants) and the Biobank Japan (roughly 180,000 participants). The East Asian variant is rare in other populations.
“Our results suggest that loss of function of CHRNB3 significantly associates with daily cigarette smoking,” the study authors wrote. This finding proposes that inhibiting the β3 subunit of nicotinic acetylcholine receptors could be a potential therapeutic approach for treating nicotine addiction.
Researchers caution that further investigation is needed to fully understand the relationship between these genetic variants and nicotine dependence. Larger studies and more detailed clinical assessments of nicotine addiction are planned to evaluate the potential of targeting CHRNB3 for therapeutic intervention.
