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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

The Pharmacogenomics Journal volume 6, pages 194–199 (2006)Cite this article

Abstract

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.

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Acknowledgements

We acknowledge Candice Schwebel for administrative assistance and Bernard Lo and Andrew Weller for technical contributions. This research was supported by a National Cancer Institute and National Institute of Drug Abuse Transdisciplinary Tobacco Use Research Center grant P5084718 to CL. JPD is supported by a National Institutes on Drug Abuse Fellowship Grant # T32 DA07241-12. Dr Berrettini is a consultant to Glaxo Smithkline.

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Authors and Affiliations

  1. Department of Psychiatry, Center for Neurobiology and Behavior, University of Pennsylvania, Philadelphia, PA, USA

    J P Dahl & W H Berrettini

  2. Department of Psychiatry and Abramson Cancer Center, Tobacco Use Research Center, University of Pennsylvania, Philadelphia, PA, USA

    C Jepson, E P Wileyto, F Patterson & C Lerman

  3. Department of Pharmacology, Pennsylvania State University College of Medicine, Hershey, PA, USA

    R Levenson

Authors
  1. J P Dahl
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  2. C Jepson
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  3. R Levenson
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  4. E P Wileyto
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  5. F Patterson
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  6. W H Berrettini
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  7. C Lerman
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Correspondence to C Lerman.

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Dahl, J., Jepson, C., Levenson, R. et al. 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. Pharmacogenomics J 6, 194–199 (2006). https://doi.org/10.1038/sj.tpj.6500358

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