Dopamine D2 receptor Taq A1 allele predicts treatment compliance of LG839 in a subset analysis of pilot study in the Netherlands

Kenneth Blum, Thomas J.H. Chen, Amanda L.C. Chen, Patrick Rhoades, Thomas J. Prihoda, B. William Downs, Debasis Bagchi, Manashi Bagchi, Seth H. Blum, Lonna Williams, Eric R. Braverman, Mallory Kerner, Roger L. Waite, Brien Quirk, Lisa White, Jeffrey Reinking

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23 Scopus citations

Abstract

Various types of individuals having "Reward Deficiency Syndrome (RDS)" related behaviors including sugar craving (e.g. obesity) have been described and heredity has been shown to be involved in some of these types. An important role of the mesolimbic dopamine system has been suggested in the reinforcing effects of a number of addictive substances (i.e. alcohol, nicotine, sugar etc) and recent molecular genetic studies are implicating the gene for the dopamine receptor (DRD2) as well as other genes in RDS and in particular obesity. We genotyped 1,058 Dutch subjects for polymorphisms of four candidate genes (PPAR gamma 2, MTHFR, 5-HT2a, and DRD2) receiving the experimental DNA-customized nutraceutical LG839. In a subset of 27 subjects having a similar genotype pattern of the entire sample, and of all the outcomes and gene polymorphisms, only the DRD2 gene polymorphism (A1 allele vs. A2 allele) had a significant Pearson correlation with days on treatment (r=0.42, p=0.045). Compared to the DRD2 A1 carriers the number of days in treatment with LG839 was 51.9±9.9 SE (95% CI, 30.8 to 73.0) and for the DRD2 A1+ carriers the number of days on treatment with LG839 was 110.6±31.1 (95% CI, 38.9 to 182.3 ). Thus the attrition was highest in the A1- genotype group. Thus, the genotype may be a predictor of treatment persistency and compliance. The feasibility of a pharmacogenetic approach in treating certain types of obesity related behaviors is cautiously suggested and warrants rigorous larger studies for confirmation.

Original languageEnglish (US)
Pages (from-to)129-140
Number of pages12
JournalGene Therapy and Molecular Biology
Volume12
Issue number1
StatePublished - Jun 1 2008

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Keywords

  • Aminoacids
  • Dopamine genetics
  • Drd2gene
  • LG839
  • Pharmacogenomics
  • Pharmcogenetics
  • Reward Deficiency Syndrome (RDS)

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

Cite this

Blum, K., Chen, T. J. H., Chen, A. L. C., Rhoades, P., Prihoda, T. J., Downs, B. W., Bagchi, D., Bagchi, M., Blum, S. H., Williams, L., Braverman, E. R., Kerner, M., Waite, R. L., Quirk, B., White, L., & Reinking, J. (2008). Dopamine D2 receptor Taq A1 allele predicts treatment compliance of LG839 in a subset analysis of pilot study in the Netherlands. Gene Therapy and Molecular Biology, 12(1), 129-140.