Could a gene lower nicotine dependence? What a CHRNB3 variant suggests

Variants in a nicotine receptor gene are associated with a lower likelihood of heavy smoking, according to a study published in Nature Communications. The findings are based on data from populations in Mexico and validated in populations with Asian and European ancestries.

Variants in the genes encoding nicotinic acetylcholine receptors, which mediate the “rewarding” effects of nicotine on the brain, have been linked to changes in smoking behavior in individuals. For example, variants in a gene called CHRNB2, which encodes one subunit (β2) of these receptors (of which there are at least nine subunit types) have been linked to reduced likelihood of heavy smoking. However, further insights may be gained from studying the relationship between smoking frequency and variants in the genes coding for other nicotinic acetylcholine receptor subunits.

Veera Rajagopal and colleagues sequenced the genomes of 37,897 current smokers who participated in the Mexico City Prospective Study (a study into the factors affecting the health of this population). The authors identified a variant in CHRNB3 (the gene which encodes the subunit) that is associated with lower daily cigarette consumption among smokers.

Compared with individuals carrying the more common version of the gene, those with one or two copies of the variant gene smoked approximately 21% or 78% fewer cigarettes, respectively. This variant was more commonly observed among people of Indigenous Mexican ancestry than in other populations.

Similar effects involving variants in CHRNB3 were found in populations of approximately 130,000 people with European ancestry from UK Biobank and roughly 180,000 with East Asian ancestry from the Biobank Japan. The authors note that larger cohorts and more robust investigation of the clinical measures indicating nicotine dependence will be needed to fully evaluate the relationship between these variants and smoking dependency.

Together, these data indicate that genetic variants affecting the activity of CHRNB3 may reduce the number of cigarettes that smokers consume per day across diverse ancestries. This finding suggests that inhibition of the β3 subunit may be a potential therapeutic strategy for nicotine addiction.

Provided by
Regeneron Genetics Center