Genetic variation in the serotonin pathway and smoking cessation with nicotine replacement therapy: new data from the Patch in Practice trial and pooled analyses.
The serotonin pathway has been implicated in nicotine dependence and may influence smoking cessation. Therefore, 792 cigarette smokers from the Patch in Practice trial were genotyped for the tryptophan hydroxylase (TPH1 A779C), serotonin transporter (SLC6A45-HTTLPR), and 5-HT1A (HTR1A C-1019G) polymorphisms. Cox regression analysis did not demonstrate significant effects of any of the three genotypes on relapse to smoking: TPH1 (Reference AA; AC: hazard ratio (HR) 0.99, 95% confidence interval (CI) 0.78, 1.24, p=0.90; CC: HR 0.93, 95% CI 0.73, 1.18, p=0.55); 5-HTTLPR (Reference LL; SL: HR 1.01, 95% CI 0.85, 1.20, p=0.90; SS: HR 1.13, 95% CI 0.91, 1.39, p=0.27); HTR1A (Reference CC; CG: HR 1.04, 95% CI 0.86, 1.25, p=0.70; GG: HR 1.01, 95% CI 0.82, 1.24, p=0.93). Moreover, pooled analyses of data from all three extant pharmacogenetic NRT trials (N=1398) found no significant effect of 5-HTTLPR genotype on continuous abstinence at 12-week (Reference LL; SL: odds ratio (OR)=1.25, 95% CI 0.89, 1.74, p=0.19; SS: OR=1.31, 95% CI 0.86, 1.98, p=0.21) or 26-week follow-up (Reference LL; SL: OR=0.93, 95% CI 0.64, 1.33, p=0.68; SS: OR=1.00, 95% CI 0.63, 1.58, p=1.00). These data do not support a statistically or clinically significant moderating effect of these specific 5-HT pathway genetic variants on smoking cessation. However, the possibility remains that other variants in these or other 5-HT genes may influence NRT efficacy for smoking cessation in treatment seeking smokers.
David
Sean P
SP
Department of Family Medicine, Center for Primary Care & Prevention, The Warren Alpert Medical School of Brown University, 111 Brewster Street, Pawtucket, RI 02806, USA. Sean_David@Brown.edu
Johnstone
Elaine C
EC
Murphy
Michael F G
MF
Aveyard
Paul
P
Guo
Boliang
B
Lerman
Caryn
C
Munafò
Marcus R
MR
D000279:Administration, Cutaneous; D000328:Adult; D000483:Alleles; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D009538:Nicotine / Q000008:administration & dosage* / Q000009:adverse effects; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D016540:Smoking Cessation; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy / Q000235:genetics; D014029:Tobacco Use Disorder / Q000235:genetics* / Q000534:rehabilitation; D016896:Treatment Outcome; D014365:Tryptophan Hydroxylase / Q000235:genetics*
C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D009538:Nicotine; C497467:TPH1 protein, human; D014365:Tryptophan Hydroxylase