DISTRIBUTION OF DOPAMINE PATHWAY GENE POLYMORPHISMS IN SUBJECTS WITH DIFFERENT SMOKING BEHAVIOR
Authors: Imyanitov *Evgeny N , Mitiushkina Natalia V , Sukhovskaya Olga A 
Published: February 2025

Abstract

Background
Multiple lines of evidence support the role of genetic constitution in the initiation, persistence, intensity and success in cessation of tobacco smoking. Switching to less harmful tools for nicotine delivery may serve as a balanced strategy to reduce the health risks for severe tobacco addicts.

Aims & Objectives
This study questioned whether genetic variations in dopamine pathway influence the interest to smoking initiation as well as the transition from occasional to habitual smoking.

Methods
The investigation included 1230 subjects (570 current smokers; 246 former smokers; 267 non- smokers, who tried cigarettes at least ones but did not become a smoker; and 147 never-smokers, who did not even attempt to taste tobacco products). The group of former smokers included 54 subjects, whose cessation interval was lower than 6 months; these cases were excluded when comparing former smokers against current smokers. Twenty gene polymorphisms, which belong to the dopamine pathway and demonstrated evidence for functional role in in vitro or in vivo studies, have been selected for investigation and analyzed in the above groups.

Results
Three groups of comparisons were performed. First, we compared never-smokers, i.e. people who never even attempted to smoke, against the rest of the study. This comparison aimed to reveal whether variations in dopamine pathway genes are involved in the interest to smoking. Secondly, we compared non-smokers versus habitual (former and current) smokers. This comparison addressed the question whether some of the studied genes influence the transition from occasional to habitual smoking. Thirdly, we analyzed genotypes of former smokers with cessation period exceeding 6 months in comparison with current smokers. If p value is 0.05, 3 out of total 60 comparisons will pass this threshold solely due to a chance. In fact, there were 13 comparisons with p &lt;0.05, which indicates that at least some of the observed associations are indeed relevant to smoking behavior. There were statistically significant differences between never- versus ever-smokers (p = 0.021) and between non-smokers versus habitual former or current smokers (p = 0.029). In contrast, the difference between former and current smokers did not reach statistical significance. Two gene polymorphisms showed consistent associations across all three comparisons, i.e., DAT1 40-bp repeat and MAOA 30-nucleotide repeat.

Discussion & Conclusion
This study confirms that genetic constitution influences the interest to smoking initiation as well as the transition from occasional to habitual smoking. Subjects with unfavorable genotypes may constitute an especial group of people requiring personalized strategies for smoking harm reduction. The analysis of dopamine pathway polymorphisms deserves to be extended to subjects with modern smoking attitudes, e.g., to the current and former users of electronic nicotine delivery systems.

Acknowledgments
This work has been supported by the Russian Science Foundation (grant 23-45-10038)