Abstract
Objective: To investigate the effects of genetic polymorphisms of human nicotinic acetylcholine receptor subunits α3, α4 and α5, which are encoded by CHRNA3, CHRNA4 CHRNA5 genes, respectively, on nicotine addiction and outcomes of pharmacological treatments for smoking cessation. Methods: A total of 143 smokers and 130 non-smokers were included. Genotyping for CHRNA3 rs578776, CHRNA4 rs1044396-rs1044397, CNRNA5 rs16969968 polymorphisms was performed by PCR, flowed by RFLP. Clinical outcomes and success rates of pharmacological treatments for smoking cessation with nicotine replacement therapy (NRT), bupropion or varenicline were determined at the 12th week of the treatment. Results: Overall, 52 out of 143 (36.4%) smokers who received pharmacotherapy were able to quit smoking. Success rates for smoking cessation were similar for female (30.3%) and male (41.6%) subjects (p = 0.16). The success rate for smoking cessation treatment with varenicline (58.5%) was significantly higher as compared to other treatments with NRT (20.0%), bupropion (32.3%) or bupropion + NRT (40.0%) (chi-square test, p = 0.001). Smoker vs. non-smoker status and the clinical outcomes of drugs used for smoking cessation were found similar in subjects carrying wild-type and variant alleles of human nicotinic acetylcholine receptor α subunits. Conclusion: In this study, smoking cessation treatment with varenicline was significantly more effective than treatments with nicotine replacement or bupropion in a cohort of Turkish subjects. Smoker/non-smoker status and the clinical outcomes of treatment with pharmacological agents were similar in subjects with wild-type or variant alleles for human nicotinic acetylcholine receptor subunits α3 (CHRNA3), α4 (CHRNA4) and α5 (CHRNA5).
Highlights
Nicotine exerts its abusive effects by stimulating neuronal nicotinic acetylcholine receptors and by participating in cholinergic system functions, which regulate emotion, cognition and rewarding effects. nAChRs are ligand-gated ion channels consisting of five subunits that modulate the release of neurotransmitters (Wen et al, 2016)
We previously examined the effects of genetic polymorphisms of a few pharmacokinetic targets, namely metabolizing enzymes of CYP2A6, CYP2B6, and the drug transporter ABCB1 (MDR1) on smoking status and success of smoking cessation therapies in a similar but smaller cohort of Turkish subjects (Muderrisoglu et al, 2020)
Within a population of Turkish subjects with an extended number of patients we aimed to investigate the effects of polymorphic variants of a few pharmacodynamics targets; namely human nicotinic acetylcholine receptor subunits α3, α4 and α5 on smoking status and the clinical outcomes of smoking cessation with pharmacotherapies
Summary
Nicotine dependence is a very serious health problem and a leading cause of preventable death in many countries. There is an increase in cigarette consumption rates both in the world (WHO, 2021) and in Turkey. 26.5% of the total population of Turkey were reported as smokers in 2016 (TSI, 2016). 58,631 smokers and, 7,941 non-smokers died because of smoking-related causes (Institute of Health Metrics and Evaluation (IHME), 2016). NAChRs are ligand-gated ion channels consisting of five subunits that modulate the release of neurotransmitters (Wen et al, 2016). Upregulation of nAChRs, α4β2 sub-type is important in the development of nicotine addiction (Miwa et al, 2011). Α3 and α5 auxiliary subunits play a role in the modulation of addiction (Fowler et al, 2011)
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