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

Research output: Contribution to journalArticle

23 Citations (Scopus)

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 2008

Fingerprint

Dopamine D2 Receptors
Netherlands
Alleles
Obesity
Genes
Genotype
Reward
Sugar Alcohols
Therapeutics
Heredity
PPAR gamma
Pharmacogenetics
Dopamine Receptors
Dietary Supplements
Nicotine
varespladib methyl
Compliance
Molecular Biology
Dopamine
DNA

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine

Cite this

Blum, K., Chen, T. J. H., Chen, A. L. C., Rhoades, P., Prihoda, T. J., Downs, B. W., ... 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.

Dopamine D2 receptor Taq A1 allele predicts treatment compliance of LG839 in a subset analysis of pilot study in the Netherlands. / Blum, Kenneth; Chen, Thomas J H; Chen, Amanda L C; Rhoades, Patrick; Prihoda, Thomas J.; Downs, B. William; Bagchi, Debasis; Bagchi, Manashi; Blum, Seth H.; Williams, Lonna; Braverman, Eric R.; Kerner, Mallory; Waite, Roger L.; Quirk, Brien; White, Lisa; Reinking, Jeffrey.

In: Gene Therapy and Molecular Biology, Vol. 12, No. 1, 06.2008, p. 129-140.

Research output: Contribution to journalArticle

Blum, K, Chen, TJH, Chen, ALC, Rhoades, P, Prihoda, TJ, Downs, BW, Bagchi, D, Bagchi, M, Blum, SH, Williams, L, Braverman, ER, Kerner, M, Waite, RL, 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, vol. 12, no. 1, pp. 129-140.
Blum, Kenneth ; Chen, Thomas J H ; Chen, Amanda L C ; Rhoades, Patrick ; Prihoda, Thomas J. ; Downs, B. William ; Bagchi, Debasis ; Bagchi, Manashi ; Blum, Seth H. ; Williams, Lonna ; Braverman, Eric R. ; Kerner, Mallory ; Waite, Roger L. ; Quirk, Brien ; White, Lisa ; Reinking, Jeffrey. / Dopamine D2 receptor Taq A1 allele predicts treatment compliance of LG839 in a subset analysis of pilot study in the Netherlands. In: Gene Therapy and Molecular Biology. 2008 ; Vol. 12, No. 1. pp. 129-140.
@article{e5629a57ad184d01999b20df977d1a0c,
title = "Dopamine D2 receptor Taq A1 allele predicts treatment compliance of LG839 in a subset analysis of pilot study in the Netherlands",
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.",
keywords = "Aminoacids, Dopamine genetics, Drd2gene, LG839, Pharmacogenomics, Pharmcogenetics, Reward Deficiency Syndrome (RDS)",
author = "Kenneth Blum and Chen, {Thomas J H} and Chen, {Amanda L C} and Patrick Rhoades and Prihoda, {Thomas J.} and Downs, {B. William} and Debasis Bagchi and Manashi Bagchi and Blum, {Seth H.} and Lonna Williams and Braverman, {Eric R.} and Mallory Kerner and Waite, {Roger L.} and Brien Quirk and Lisa White and Jeffrey Reinking",
year = "2008",
month = "6",
language = "English (US)",
volume = "12",
pages = "129--140",
journal = "Gene Therapy and Molecular Biology",
issn = "1529-9120",
publisher = "Gene Therapy and Molecular Biology",
number = "1",

}

TY - JOUR

T1 - Dopamine D2 receptor Taq A1 allele predicts treatment compliance of LG839 in a subset analysis of pilot study in the Netherlands

AU - Blum, Kenneth

AU - Chen, Thomas J H

AU - Chen, Amanda L C

AU - Rhoades, Patrick

AU - Prihoda, Thomas J.

AU - Downs, B. William

AU - Bagchi, Debasis

AU - Bagchi, Manashi

AU - Blum, Seth H.

AU - Williams, Lonna

AU - Braverman, Eric R.

AU - Kerner, Mallory

AU - Waite, Roger L.

AU - Quirk, Brien

AU - White, Lisa

AU - Reinking, Jeffrey

PY - 2008/6

Y1 - 2008/6

N2 - 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.

AB - 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.

KW - Aminoacids

KW - Dopamine genetics

KW - Drd2gene

KW - LG839

KW - Pharmacogenomics

KW - Pharmcogenetics

KW - Reward Deficiency Syndrome (RDS)

UR - http://www.scopus.com/inward/record.url?scp=50849101695&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=50849101695&partnerID=8YFLogxK

M3 - Article

AN - SCOPUS:50849101695

VL - 12

SP - 129

EP - 140

JO - Gene Therapy and Molecular Biology

JF - Gene Therapy and Molecular Biology

SN - 1529-9120

IS - 1

ER -