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Published on: February 10, 2012
Pharmacogenetic study of seven polymorphisms in three nicotinic acetylcholine receptor subunits in smoking-cessation
Giulia Pintarelli1, Antonella Galvan2, Paolo Pozzi3,4
1Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Abstract:
Smoking-cessation therapy reduces the risk of smoking-related diseases, but is successful only in a fraction of smokers. There is growing evidence that genetic variations in nicotinic acetylcholine receptor (nAChR) subunits influence the risk of nicotine dependence and the ability to quit smoking. To investigate the role of polymorphisms in nAChR genes on smoking quantity and the outcome of smoking-cessation therapies, we carried out an association study on 337 smokers who underwent pharmacotherapy with varenicline, bupropion, nicotine replacement therapy (NRT) alone, or NRT plus bupropion. Smoking habit and abstention were assessed from the number of cigarettes smoked per day (CPD) and the exhaled CO (eCO), at baseline and up to 12 months. We genotyped seven polymorphisms in genes encoding the nAChR subunits CHRNA4, CHRNA5, and CHRNB2. At baseline, both CPD and eCO were associated with polymorphisms in the CHRNA5 locus (rs503464, rs55853698, rs55781567 and rs16969968; P < 0.01). rs503464, a variant in the 5'-UTR of CHRNA5, was also associated with short-, mid- and long-term responses to therapy (P = 0.011, P = 0.0043, P = 0.020, respectively), although after correction for multiple testing only the association at the mid-term assessment remained significant (FDR = 0.03). These data support the role of individual genetic makeup in the ability to quit smoking.
Insights
Genetic variations in nicotinic acetylcholine receptor (nAChR) genes impact smoking habits and quitting success. Specific CHRNA5 gene polymorphisms influence smoking quantity and response to cessation therapies like varenicline and bupropion.
Area of Science:
- Pharmacogenetics
- Addiction Science
- Genetics
Background:
- Smoking cessation therapies improve health but have limited success rates.
- Genetic factors, particularly variations in nicotinic acetylcholine receptor (nAChR) subunits, are increasingly recognized as influencing nicotine dependence and smoking cessation outcomes.
Purpose of the Study:
- To investigate the association between polymorphisms in nAChR genes and smoking quantity.
- To determine the role of these genetic variations in the effectiveness of smoking-cessation pharmacotherapies.
Main Methods:
- An association study was conducted on 337 smokers undergoing pharmacotherapy (varenicline, bupropion, NRT, or combination).
- Smoking habits were assessed via cigarettes per day (CPD) and exhaled carbon monoxide (eCO).
- Seven polymorphisms in CHRNA4, CHRNA5, and CHRNB2 genes were genotyped.
Main Results:
- Baseline CPD and eCO levels were significantly associated with polymorphisms in the CHRNA5 locus.
- A specific variant (rs503464) in the CHRNA5 5'-UTR region showed associations with short-, mid-, and long-term treatment responses.
- After multiple testing correction, the association between rs503464 and mid-term cessation response remained statistically significant (FDR = 0.03).
Conclusions:
- Individual genetic makeup, specifically variations in nAChR genes like CHRNA5, plays a role in an individual's ability to quit smoking.
- These findings suggest potential for personalized approaches to smoking cessation based on genetic profiles.
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