PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-3 (3)
 

Clipboard (0)
None
Journals
Authors
more »
Year of Publication
Document Types
1.  The DRD4 Exon III VNTR, Bupropion, and Associations With Prospective Abstinence 
Nicotine & Tobacco Research  2012;15(7):1190-1200.
Introduction:
DRD4 Exon III Variable Number of Tandem Repeat (VNTR) variation was found to interact with bupropion to influence prospective smoking abstinence, in a recently published longitudinal analyses of N = 331 individuals from a randomized double-blind placebo-controlled trial of bupropion and intensive cognitive–behavioral mood management therapy.
Methods:
We used univariate, multivariate, and longitudinal logistic regression to evaluate gene, treatment, time, and interaction effects on point prevalence and continuous abstinence at end of treatment, 6 months, and 12 months, respectively, in N = 416 European ancestry participants in a double-blind pharmacogenetic efficacy trial randomizing participants to active or placebo bupropion. Participants received 10 weeks of pharmacotherapy and 7 sessions of behavioral therapy, with a target quit date 2 weeks after initiating both therapies. VNTR genotypes were coded with the long allele dominant resulting in 4 analysis categories. Covariates included demographics, dependence measures, depressive symptoms, and genetic ancestry. We also performed genotype-stratified secondary analyses.
Results:
We observed significant effects of time in longitudinal analyses of both abstinence outcomes, of treatment in individuals with VNTR long allele genotypes for both abstinence outcomes, and of covariates in some analyses. We observed non-significantly larger differences in active versus placebo effect sizes in individuals with VNTR long allele genotypes than in individuals without the VNTR long allele, in the directions previously reported.
Conclusions:
VNTR by treatment interaction differences between these and previous analyses may be attributable to insufficient size of the replication sample. Analyses of multiple randomized clinical trials will enable identification and validation of factors mediating treatment response.
doi:10.1093/ntr/nts245
PMCID: PMC3682839  PMID: 23212438
2.  Pharmacogenetic Smoking Cessation Intervention in a Health Care Setting: A Pilot Feasibility Study 
Nicotine & Tobacco Research  2012;15(2):518-526.
Introduction:
There is increasing evidence that response to pharmacological treatment for nicotine dependence may be moderated by genetic polymorphisms. However, the feasibility, acceptability, and impact of genetically tailoring treatment in real-world clinical settings are unknown.
Methods:
We conducted a multiphased, mixed-methods feasibility study with current smokers to develop and evaluate a patient-centered, theoretically grounded personalized medicine treatment protocol. The initial research phase included formative work to develop intervention materials. The second phase included a randomized pilot trial to evaluate the intervention. Trial participants (n = 36) were genotyped for ANKK1 rs1800497 and were randomized to receive genetic feedback (GF) plus standard behavioral counseling (BC) for smoking cessation or BC without GF. All participants received genetically tailored pharmacotherapy (nicotine patch or bupropion).
Results:
The intervention was feasible to implement and was acceptable to participants based on satisfaction ratings and objective measures of participation. There was no evidence that the GF resulted in adverse psychological outcomes (e.g., depression, fatalism, reduced perceived control over quitting, differential motivation for quitting) based on quantitative or qualitative outcomes.
Conclusions:
Study results suggest that it is feasible to offer treatment within a health care setting that includes genetically tailored pharmacotherapy and doing so had no apparent adverse psychological impacts. Further evaluation of pharmacogenetically tailored smoking cessation interventions appears warranted.
doi:10.1093/ntr/nts173
PMCID: PMC3611995  PMID: 22949583
3.  Association of the Nicotine Metabolite Ratio and CHRNA5/CHRNA3 Polymorphisms With Smoking Rate Among Treatment-Seeking Smokers 
Nicotine & Tobacco Research  2011;13(6):498-503.
Introduction:
Genome-wide association studies have linked single-nucleotide polymorphisms (SNPs) in the CHRNA5/A3/B4 gene cluster with heaviness of smoking. The nicotine metabolite ratio (NMR), a measure of the rate of nicotine metabolism, is associated with the number of cigarettes per day (CPD) and likelihood of cessation. We tested the potential interacting effects of these two risk factors on CPD.
Methods:
Pretreatment data from three prior clinical trials were pooled for analysis. One thousand and thirty treatment seekers of European ancestry with genotype data for the CHRNA5/A3/B4 SNPs rs578776 and rs1051730 and complete data for NMR and CPD at pretreatment were included. Data for the third SNP, rs16969968, were available for 677 individuals. Linear regression models estimated the main and interacting effects of genotype and NMR on CPD.
Results:
We confirmed independent associations between the NMR and CPD as well as between the SNPs rs16969968 and rs1051730 and CPD. We did not detect a significant interaction between NMR and any of the SNPs examined.
Conclusions:
This study demonstrates the additive and independent association of the NMR and SNPs in the CHRNA5/A3/B4 gene cluster with smoking rate in treatment-seeking smokers.
doi:10.1093/ntr/ntr012
PMCID: PMC3103715  PMID: 21385908

Results 1-3 (3)