Determining the Impact of the Interactions of CYP2B6*6 and CYP2A6 Polymorphisms on the Treatment of Nicotine Dependence

Introduction: Nicotine metabolising enzymes CYP2B6 and CYP2A6 are implicated in the treatment of nicotine addiction.Even though evidence suggests they may interact to influence nicotine dependence treatment outcomes in terms of nicotine dependence and withdrawal syndromes, as well as therapy types (placebo, bupropion, and NRT), the importance of their interaction in nicotine cessation has yet to be fully substantiated and clarified.

Methods: A total of 1862 people were analysed, including Caucasians and African Americans. The Fagerström Test for Nicotine Dependency (FTND) and Wisconsin Inventory of Smoking Dependence Motives (WISDM) measures were used to assess nicotine dependence and withdrawal syndrome, respectively. Participants were needed to smoke at least ten cigarettes per day and to use one of three types of therapy (placebo, NRT, or bupropion) for two weeks before reporting their quitting status six months later. Participants were also screened for SNPs CYP2A6*1A (rs1137115), *1H (rs616636070),*4A (rs28399434), *9A (rs28399443),*12A (rs28399442), and CYP2B6*6(rs3745274) for nicotine genotype analysis.

Results: The chi-squared test revealed that gene variations were consistently distributed in the population withp-values > 0.05. According to logistic regression analysis, CYP2A6*4A was most significantly associated with the odds ratio (OR) of quitting smoking in each treatment group with nicotine dependence syndrome (OR=1.61, 95% CI 1.31-1.96), and *4A in individuals with nicotine withdrawal syndrome (OR=1.70, 95% CI 1.15-1.95). In the bupropion group, the ANOVA test revealed a significant main interaction effect between CYP2B6*6, *1A, *4A, and *12A gene variants.

Conclusion: CYP2A6 and CYP2B6*6 may interact to improve the chances of nicotine addiction treatment success.