Cytochrome P450 2A6 and 2B6 polymorphisms and smoking cessation success in patients treated with varenicline

Tomaz, Paulo Roberto Xavier; Kajita, Mariana Soares; Santos, Juliana Rocha; Scholz, Jaqueline; Abe, Tânia Ogawa; Gaya, Patrícia Viviane; Krieger, José Eduardo; Pereira, Alexandre C.; Santos, Paulo Caleb Júnior Lima

doi:10.1007/s00228-019-02731-z

Cited by 7 publications

(8 citation statements)

References 27 publications

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“…Seven studies were removed during full article review because incorrect study designs (e.g., a focus on the use of mouse models, meta-analysis, or outcome not focused on smoking abstinence). Results from a final total of 79 articles are summarized ( Figure 1 )) ( Bergen et al, 2014 ; Breitling et al, 2010 ; Chen et al, 2012 ; Cameli et al, 2018 ; Chen et al, 2014 ; Chen et al, 2015 ; Cinciripini et al, 2004 ; Dahl et al, 2006 ; David et al, 2007b ; David et al, 2007a ; David et al, 2008b ; David et al, 2008a ; David et al, 2013 ; El-Boraie et al, 2020 ; Glatard et al, 2017 ; Gold et al, 2012 ; Guo & Heitjan, 2010 ; Heitjan et al, 2008b ; Ho et al, 2009 ; Hutchison et al, 2007 ; Johnstone et al, 2004 ; Johnstone et al, 2007 ; Lee et al, 2007 ; Lee et al, 2012 ; Lerman et al, 2002 ; Lerman et al, 2003 ; Lerman et al, 2004 ; Lerman et al, 2006 ; Lerman et al, 2010 ; Leventhal et al, 2012 ; Munafò et al, 2007 ; Munafò et al, 2009 ; Munafò et al, 2013 ; Quintana & Conti, 2013 ; Robinson et al, 2007 ; Rocha Santos et al, 2015 ; Roche et al, 2019 ; Rose et al, 2010 ; Swan et al, 2005 ; Swan et al, 2007 ; Swan et al, 2012 ; Tomaz et al, 2015 ; Tomaz et al, 2018 ; Tomaz et al, 2019 ; Santos et al, 2020 ; Ton et al, 2007 ; Tyndale et al, 2015 ; Uhl et al, 2008 ; Verde et al, 2014 ; Ware et al, 2015 ; Zhu et al, 2012 ; Zhu et al, 2014a ; Zhu et al, 2014b ) and 18 (23%) estimated genetic ancestry categories ( Hu et al, 2006...…”

Section: Resultsmentioning

confidence: 99%

A scoping review of smoking cessation pharmacogenetic studies to advance future research across racial, ethnic, and ancestral populations

Prom-Wormley,

Wells,

Landes

et al. 2023

Front. Genet.

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Abstinence rates among smokers attempting to quit remain low despite the wide availability and accessibility of pharmacological smoking cessation treatments. In addition, the prevalence of cessation attempts and abstinence differs by individual-level social factors such as race and ethnicity. Clinical treatment of nicotine dependence also continues to be challenged by individual-level variability in effectiveness to promote abstinence. The use of tailored smoking cessation strategies that incorporate information on individual-level social and genetic factors hold promise, although additional pharmacogenomic knowledge is still needed. In particular, genetic variants associated with pharmacological responses to smoking cessation treatment have generally been conducted in populations with participants that self-identify as White race or who are determined to be of European genetic ancestry. These results may not adequately capture the variability across all smokers as a result of understudied differences in allele frequencies across genetic ancestry populations. This suggests that much of the current pharmacogenetic study results for smoking cessation may not apply to all populations. Therefore, clinical application of pharmacogenetic results may exacerbate health inequities by racial and ethnic groups. This scoping review examines the extent to which racial, ethnic, and ancestral groups that experience differences in smoking rates and smoking cessation are represented in the existing body of published pharmacogenetic studies of smoking cessation. We will summarize results by race, ethnicity, and ancestry across pharmacological treatments and study designs. We will also explore current opportunities and challenges in conducting pharmacogenomic research on smoking cessation that encourages greater participant diversity, including practical barriers to clinical utilization of pharmacological smoking cessation treatment and clinical implementation of pharmacogenetic knowledge.

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Section: Resultsmentioning

confidence: 99%

A scoping review of smoking cessation pharmacogenetic studies to advance future research across racial, ethnic, and ancestral populations

Prom-Wormley,

Wells,

Landes

et al. 2023

Front. Genet.

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“…Wassenaar et al 18 observed a higher quantity of cigarettes consumed per day by individuals possessing normal metabolizer genes in comparison with those having slow metabolizers. Although other studies have not reported the same association 74 or even divergent results 75,76 , several works have shown a direct association between the CYP2A6 genotype of lower enzyme activity and the lower risk of becoming a smoker, less nicotine dependence, fewer cigarettes consumed and greater success in cessation [17][18][19][20][21] .…”

Section: Polymorphism Of Cyp2a6mentioning

confidence: 98%

Genetic variability in the neurobiology of nicotine dependence: effects on smoking behavior

et al. 2023

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Background: Smoking dependence is a chronic disease and a public health problem. The neurobiology of nicotine addiction can explain smoking behavior. This system has genetic variability that has been associated with vulnerability to dependence. Genetic variability in the neurobiology of smoking can help to understand why individuals exposed to drugs may or may not become addicted. Objective: This study aims to address genetic variability in the neurobiology of smoking addiction with a focus on polymorphic genes related to the nicotinic response and the dopaminergic reward pathway. Method: This work involved a search of the main scientific research on genetic variability in the neurobiology of smoking and its effects on smoking behavior. One hundred and five studies were selected, most of which highlighted polymorphisms in the genes of nicotinic receptors, dopamine receptors, and nicotine metabolism. Results: The majority of studies have focused on genes related to the activation of the dopaminergic reward system by nicotine. Combinations between different polymorphisms were also highlighted, showing that interactions can determine a genetic profile of predisposition to smoking addiction. Additionally, gender and ethnicity were identified as relevant factors. Conclusion: Knowledge of the genetic bases involved in the individual response to smoking can enable a better understanding of inter-individual differences in smoking behavior, and contribute to improving the treatment of addiction.

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“…Exclusion criteria were: patients with hepatic, renal and gastrointestinal disorders that compromised drug metabolism and elimination; patients who had taken cytochrome P450 enzymeinducing or inhibiting drugs in the previous 6 weeks; alcoholic patients and drug users; those with unstable psychiatric illnesses; women at risk of pregnancy; patients with contraindications to the treatment with varenicline mentioned above. Interindividual variability in response to drugs for smoking cessation suggests that treatments may be more effective in subgroups of smokers [12][13][14][15]. In the context of personalized medicine, researchers have sought to identify predictors of response to smoking cessation treatments, which are generally involved in pharmacokinetic and/or pharmacodynamic pathways, such as genetic factors, gene expression profiles, proteins and metabolites [16][17][18][19].…”

Section: Patient Samplementioning

confidence: 99%

“…Interindividual variability in response to drugs for smoking cessation suggests that treatments may be more effective in subgroups of smokers [12][13][14][15]. In the context of personalized medicine, researchers have sought to identify predictors of response to smoking cessation treatments, which are generally involved in pharmacokinetic and/or pharmacodynamic pathways, such as genetic factors, gene expression profiles, proteins and metabolites [16][17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Profile of the Nicotinic Cholinergic Receptor Alpha 7 Subunit Gene Expression is Associated with Response to Varenicline Treatment

Santos

Tomaz

Scholz

et al. 2020

Genes

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Introduction: Smoking is considered the leading cause of preventable morbidity and mortality worldwide. Studies have sought to identify predictors of response to smoking cessation treatments. The aim of this study was to analyze a possible association of target gene expression for smoking cessation with varenicline. Methods: We included 74 smokers starting treatment with varenicline. Gene expression analysis was performed through the custom RT² Profiler qPCR array assay, including 17 genes. Times for sample collection were before the start of therapy (T0) and two weeks (T2) and four weeks (T4) after the start of treatment. Results: For gene expression analysis, we selected 14 patients who had success and 13 patients resistant to varenicline treatment. Success was considered to be when a patient achieved tobacco abstinence until the fourth week of treatment and resistant was when a patient had not stopped smoking as of the fourth week of treatment. We observed a significant difference for CHRNA7 gene expression: in the resistant group, samples from T2 and T4 had lower expression compared with T0 (fold change: 0.38, P = 0.007; fold change: 0.67, P = 0.004; respectively). Conclusion: This exploratory clinical study, searching for a possible predictor of effectiveness for varenicline, reaffirmed the association of the α7 nAChR subunit for nicotine dependence and smoking therapy effectiveness with varenicline.

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Cytochrome P450 2A6 and 2B6 polymorphisms and smoking cessation success in patients treated with varenicline

Cited by 7 publications

References 27 publications

A scoping review of smoking cessation pharmacogenetic studies to advance future research across racial, ethnic, and ancestral populations

A scoping review of smoking cessation pharmacogenetic studies to advance future research across racial, ethnic, and ancestral populations

Genetic variability in the neurobiology of nicotine dependence: effects on smoking behavior

Profile of the Nicotinic Cholinergic Receptor Alpha 7 Subunit Gene Expression is Associated with Response to Varenicline Treatment

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