Genetic variation (CHRNA5), medication (combination nicotine replacement therapy vs. varenicline), and smoking cessation.
- Authors
- Chen, Li-Shiun; Baker, Timothy B; Jorenby, Douglas; Piper, Megan; Saccone, Nancy; Johnson, Eric; Breslau, Naomi; Hatsukami, Dorothy; Carney, Robert M; Bierut, Laura J
- Year
- 2015
- Journal
- Drug and alcohol dependence
- PMID
- 26142345
- DOI
- 10.1016/j.drugalcdep.2015.06.022
- PMCID
- PMC4537319
OBJECTIVE: Recent evidence suggests that the efficacy of smoking cessation pharmacotherapy can vary across patients based on their genotypes. This study tests whether the coding variant rs16969968 in the CHRNA5 nicotinic receptor gene predicts the effects of combination nicotine replacement therapy (cNRT) and varenicline on treatment outcomes. METHOD: In two randomized smoking cessation trials comparing cNRT vs. placebo, and varenicline vs. placebo, we used logistic regression to model associations between CHRNA5 rs16969968 and abstinence at end of treatment. RESULTS: For abstinence at end of treatment, there was an interaction between cNRT and rs16969968 (X(2)=8.15, df=2, omnibus-p=0.017 for the interaction); individuals with the high-risk AA genotype were more likely to benefit from cNRT. In contrast, varenicline increased abstinence, but its effect did not vary with CHRNA5. However, the genetic effects differed between the placebo control groups across two trials (wald=3.94, df=1, p=0.047), this non-replication can alter the interpretation of pharmacogenetic findings. CONCLUSIONS: Results from two complementary smoking cessation trials demonstrate inconsistent genetic results in the placebo arms. This evidence highlights the need to compare the most effective pharmacotherapies with the same placebo control to establish pharmacogenetic evidence to aid decisions on medication choice for patients trying to quit smoking.
Medication efficacy on abstinence EOT and CHRNA5 rs16969968 genotypes: UW-TTURC trial shows that combination NRT increases abstinence EOT in genotypes GA and AA, but not GG. Varenicline trial shows that varenicline increases abstinence across genotypes.Genotypic effects in the placebo groups differ between these two trials.aUW-TTURC trial: Combination NRT increases abstinence(OR=3.17, 95% CI=1.99–5.05, df=1, p= 8.1×10−6). A significant interaction between treatment (placebo versus combination NRT) and rs16969968 genotypes (X2=8.15, df=2, omnibus-p=0.017 for the interaction).bVarenicline trial: Varenicline increases abstinence (OR=4.18, 95% CI=3.05–5.72, df=1, p=5.5×10−19).The CHRNA5 rs16969968 genotypic effects on abstinence in the placebo groups differ significantly between the two studies (rs16969968*Study Interaction Wald=3.94, df=1, p=0.047). There is a genotypic effect in the UW-TTURC trial placebo arm, but not in the varenicline trial placebo arm.NNT: number needed to treat
| # | Section | Preview |
|---|---|---|
| 20 | 4. DISCUSSION | The results of this study should be interpreted in the context of several limitations. First, the… |
| 21 | 4. DISCUSSION | In summary, this work highlights the challenges and needed evidence to translate genetic research… |
No entities extracted from this document yet.
No uploaded files.
No papers in this knowledge base cite this source.
External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| Exploring Predictors of Treatment Response to GLP-1 Receptor Agonists for Smoking Cessation. | Yammine L et al. | — | 2025 | → |
| Nicotine Abuse and Neurodegeneration: Novel Pharmacogenetic Targets to Aid Quitting and Reduce the Risk of Dementia. | Almahasneh F et al. | — | 2024 | → |
| A scoping review of smoking cessation pharmacogenetic studies to advance future research across racial, ethnic, and ancestral populations. | Prom-Wormley EC et al. | — | 2023 | → |
| CHRNA5-A3-B4 and DRD2 Genes and Smoking Cessation Throughout Adulthood: A Longitudinal Study of Women. | Jones SK et al. | — | 2023 | → |
| Nicotine receptor partial agonists for smoking cessation. | Livingstone-Banks J et al. | — | 2023 | → |
| A systematic review of genetic variation within nicotinic acetylcholine receptor genes and cigarette smoking cessation. | Jones SK et al. | — | 2022 | → |
| Medication adherence and rate of nicotine metabolism are associated with response to treatment with varenicline among smokers with HIV. | Bauer AM et al. | — | 2021 | → |
| Proof of Concept of a Personalized Genetic Risk Tool to Promote Smoking Cessation: High Acceptability and Reduced Cigarette Smoking. | Ramsey AT et al. | — | 2021 | → |
| Genetic Variant in CHRNA5 and Response to Varenicline and Combination Nicotine Replacement in a Randomized Placebo-Controlled Trial. | Chen LS et al. | — | 2020 | → |
| Variants in the CHRNA5-CHRNA3-CHRNB4 Region of Chromosome 15 Predict Gastrointestinal Adverse Events in the Transdisciplinary Tobacco Use Research Center Smoking Cessation Trial. | Culverhouse RC et al. | — | 2020 | → |
| Compartmentalized Devices as Tools for Investigation of Human Brain Network Dynamics. | Fantuzzo JA et al. | — | 2019 | → |
| Cholinergic receptor nicotinic alpha 5 subunit polymorphisms are associated with smoking cessation success in women. | Tomaz PRX et al. | — | 2018 | → |
| From genes to treatments: a systematic review of the pharmacogenetics in smoking cessation. | Salloum NC et al. | — | 2018 | → |
| Leveraging Genomic Data in Smoking Cessation Trials in the Era of Precision Medicine: Why and How. | Chen LS et al. | — | 2018 | → |
| Neurobiological Considerations for Tobacco Use Disorder. | Chawla M et al. | — | 2018 | → |
| Pathways to precision medicine in smoking cessation treatments. | Chen LS et al. | — | 2018 | → |
| Preparing the Way: Exploiting Genomic Medicine to Stop Smoking. | Bierut LJ et al. | — | 2018 | → |
| The Value of Biosamples in Smoking Cessation Trials: A Review of Genetic, Metabolomic, and Epigenetic Findings. | Saccone NL et al. | — | 2018 | → |
| Toward the implementation of genomic applications for smoking cessation and smoking-related diseases. | Ramsey AT et al. | — | 2018 | → |
| A nanoparticle-based nicotine vaccine and the influence of particle size on its immunogenicity and efficacy. | Zhao Z et al. | — | 2017 | → |
| Association of the DBH Polymorphism rs3025343 With Smoking Cessation in a Large Population-Based Sample. | Hirvonen K et al. | — | 2017 | → |
| Genetic susceptibility variants for lung cancer: replication study and assessment as expression quantitative trait loci. | Pintarelli G et al. | — | 2017 | → |
| Innovative approaches to support smoking cessation for individuals with mental illness and co-occurring substance use disorders. | Das S et al. | — | 2017 | → |
| Oral Cell DNA Adducts as Potential Biomarkers for Lung Cancer Susceptibility in Cigarette Smokers. | Hecht SS | — | 2017 | → |
| Pharmacogenetic Optimization of Smoking Cessation Treatment. | Chenoweth MJ et al. | — | 2017 | → |
| Tobacco use disorder and treatment: new challenges and opportunities. | Ziedonis D et al. | — | 2017 | → |
| Genetic Risk Can Be Decreased: Quitting Smoking Decreases and Delays Lung Cancer for Smokers With High and Low CHRNA5 Risk Genotypes - A Meta-Analysis. | Chen LS et al. | — | 2016 | → |
| Increased nicotine response in iPSC-derived human neurons carrying the CHRNA5 N398 allele. | Oni EN et al. | — | 2016 | → |
| The CHRNA5-A3-B4 Gene Cluster and Smoking: From Discovery to Therapeutics. | Lassi G et al. | — | 2016 | → |