Interaction between variation in the D2 dopamine receptor (DRD2) and the neuronal calcium sensor-1 (FREQ) genes in predicting response to nicotine replacement therapy for tobacco dependence

We have previously demonstrated that a functional dopamine D2 receptor promoter variant (DRD2 - 141 Ins/Del) predicts response to nicotine replacement therapy (NRT). The present study extends this finding in the same population of 363 NRT-treated subjects, by examining variation in the gene encoding the neuronal calcium sensor-1 protein (FREQ), which functions to regulate D2 receptor desensitization. The results indicate a statistically significant interaction effect of DRD2 - 141 and FREQ genotypes on abstinence at the end of the NRT treatment phase; 62% of the smokers with at least one copy of the DRD2 - 141 Del allele and two copies of the FREQ rs1054879 A allele were abstinent from smoking, compared to 29-38% abstinence rates for other smokers in the trial. This result suggests that the interaction between variation in the DRD2 and FREQ genes, which both encode components of the D2 dopamine receptor signal transduction pathway, impacts the efficacy of NRT.