Lack of association of DRD2 rs1800497 (Taq1A) polymorphism with smoking cessation in a nicotine replacement therapy randomized trial.
BACKGROUND
We previously reported evidence that the T allele of the dopamine type-2 receptor (DRD2) rs1800497 polymorphism is associated with improved response to nicotine replacement therapy (NRT) relative to placebo and that this association may only be present in females. However, evidence of the poor replication validity of genetic association studies is growing, particularly among those that report subgroup analyses. We therefore attempted to replicate our previous finding of an association between the DRD2 rs1800497 genotype and response to NRT in a new, larger cohort, with greater statistical power.


METHODS
Participants were randomly assigned to one of two levels of smoking cessation behavioral support (usual care vs. weekly support). All participants received 8 weeks of 15-mg NRT transdermal patch.


RESULTS
The presence of one or more T alleles was associated with a slightly but not significantly lower likelihood of abstinence at 3 and 6 months. We found evidence of a genotype x sex interaction effect. However, stratified analyses indicated a main effect of genotype opposite to the effect reported previously, with females carrying one or more copies of the T allele less likely to be abstinent.


CONCLUSIONS
Our results do not support an association between the DRD2 rs1800497 (Taq1A) polymorphism and response to NRT, contrary to our previous study.
Munafò
Marcus R
MR
Department of Experimental Psychology, University of Bristol, 12a Priory Road, Bristol BS8 1TU, UK. marcus.munafo@bristol.ac.uk
Johnstone
Elaine C
EC
Murphy
Michael F G
MF
Aveyard
Paul
P
D000328:Adult; D000368:Aged; D000483:Alleles; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009538:Nicotine / Q000008:administration & dosage*; D010919:Placebos; D011110:Polymorphism, Genetic; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D012737:Sex Factors; D012907:Smoking / Q000628:therapy; D016540:Smoking Cessation / Q000379:methods; D014029:Tobacco Use Disorder / Q000188:drug therapy* / Q000235:genetics*; D055815:Young Adult
D010919:Placebos; D017448:Receptors, Dopamine D2; D009538:Nicotine