D2 dopamine receptor gene (DRD2) Taql A polymorphism: reduced dopamine D2 receptor binding in the human striatum associated with the A1 allele

Thompson, J; Thomas, N.; Singleton, Andrew; Piggott, Margaret A.; Lloyd, Stephen; Perry, E K; Morris, Christopher M.; Perry, R. H.; Ferrier, I. N.; Court, Jennifer A.

doi:10.1097/00008571-199712000-00006

Cited by 522 publications

(391 citation statements)

References 0 publications

Supporting

Mentioning

360

Contrasting

Unclassified

Order By: Relevance

“…The SNP has been reported to affect DRD2 availability in postmortem striatal samples ( Noble, Blum, Ritchie, Montgomery, & Sheridan, 1991 ;Thompson et al, 1997 ), and evidence from in vivo studies indicates an association between the A1 allele and lower mean relative glucose metabolic rate in dopaminergic regions in the human brain ( Noble, Gottschalk, Fallon, Ritchie, & Wu, 1997 ). Positron emission tomography (PET) scan studies have indicated that this allele also is associated with low receptor density ( Jonsson et al, 1999 ).…”

Section: Discussionmentioning

confidence: 99%

Association of the DRD2 gene Taq1A polymorphism and smoking behavior: A meta-analysis and new data

Munafò¹,

Timpson²,

David³

et al. 2009

Nicotine &Amp; Tobacco Research

View full text Add to dashboard Cite

A number of pharmacogenetic studies have suggested an association between the DRD2 gene and response to smoking cessation pharmacotherapy. Reduced-function alleles (i.e., those associated with, e.g., reduced mRNA expression) of polymorphisms in the DRD2 gene (e.g., Taq1A1) generally have been shown to predict better response to nicotine replacement Abstract Introduction: Many studies have investigated the association of the dopamine type-2 receptor ( DRD2 ) Taq1A polymorphism with tobacco use and cigarette smoking behaviors, but fi ndings remain equivocal. There is a biological basis for considering that this association differs by sex, and differences in subpopulations might explain some of the contradictory evidence.Methods: Our a priori hypothesis was that the association of the DRD2 Taq1A polymorphism with smoking behavior would be more prominent in females than males. We therefore investigated the strength of evidence for an association between the DRD2 Taq1A polymorphism and smoking behavior in a large sample of females and used meta-analytic techniques to synthesize existing published data and explore the role of sex in explaining any heterogeneity between studies. Results:We did not observe any strong evidence of association between the DRD2 Taq1A polymorphism and smoking behavior, including smoking initiation, smoking persistence, and smoking rate, either in our female sample or in our metaanalysis of 29 studies, comprising 28 published studies and the data from the present study. Metaregression suggested an association between the proportion of male participants in a study and the individual study effect size, indicating a larger effect size with a greater proportion of male participants for smoking initiation and smoking persistence. This effect did not appear to be due to the inclusion of the data from the present study.Discussion: Available evidence does not support an association between the DRD2 Taq1A polymorphism and smoking behavior. Contrary to our a priori hypothesis, we found evidence of a stronger association in males than in females.

show abstract

Section: Discussionmentioning

confidence: 99%

Association of the DRD2 gene Taq1A polymorphism and smoking behavior: A meta-analysis and new data

Munafò¹,

Timpson²,

David³

et al. 2009

Nicotine &Amp; Tobacco Research

View full text Add to dashboard Cite

show abstract

“…[22][23][24][25][26] Moreover, some of these synonymous variations have been demonstrated to affect D2 receptor expression in central nervous system, particularly in the striatum and caudate nucleus. [15][16][17][18] By contrast, although it is well established that defective dopamine signaling may result in PRL hypersecretion and lactotroph proliferation, 2 the possible association of DRD2 polymorphisms with PRL-omas has been so far disregarded. Indeed, the few studies investigating the possible relationships between PRL secretion and DRD2 variants focused on the impact of DRD2 polymorphisms on PRL levels in patients with schizophrenia during treatment with a variety of antipsychotic medications.…”

Section: Discussionmentioning

confidence: 99%

“…In particular, previous studies reported the association of DRD2 TaqI A, TaqI B and NcoI polymorphisms with modifications in D2 receptor binding and expression in human central nervous system, particularly in the striatum. [15][16][17][18] The aim of this study was to assess the possible association between four common DRD2 gene polymorphisms (that is, TaqI A1/A2, TaqI B1/B2, HphI G/T and NcoI C/T) and the efficacy of CB treatment in patients with PRL-oma.…”

Section: Introductionmentioning

confidence: 99%

Dopamine D2 receptor gene polymorphisms and response to cabergoline therapy in patients with prolactin-secreting pituitary adenomas

et al. 2008

View full text Add to dashboard Cite

Dopamine-agonist cabergoline (CB) reduces prolactin (PRL) secretion and tumor size in 80% of patients with prolactin-secreting adenomas (PRL-omas) by binding type 2 dopamine receptor (DRD2). The mechanisms responsible for resistance to CB remain largely unknown. To assess the association of DRD2 with sensitivity to CB, TaqI-A1/A2, TaqI-B1/B2, HphI-G/T and NcoI-C/T genotypes were determined in a cross-sectional retrospective study, including 203 patients with PRL-oma. DRD2 alleles frequencies did not differ between patients and 212 healthy subjects. Conversely, NcoI-T allele frequency was higher in resistant rather than responsive patients, considering both PRL normalization (56.6 vs 45.3%, P ¼ 0.038) and tumor shrinkage (70.4 vs 41.4%, P ¼ 0.006). Finally, [TaqI A1À/TaqI B1À/HphI TÀ/NcoI TÀ] haplotype was found in 34.5% of patients normalizing PRL with p3 mg/ week of CB vs 11.3% of resistants (P ¼ 0.021). In conclusion, resistance to CB was associated with DRD2 NcoI-T þ allele, consistent with evidence suggesting that this variant may lead to reduction and instability of DRD2 mRNA or protein.

show abstract

“…58 Some studies, but not all, found the TaqI A1 allele resulted in a lower density of D 2 receptors in the human striatum in vitro and in vivo. [59][60][61][62] The TaqI A1 allele may be a risk factor for a variety of smoking behaviors (Table 2); [63][64][65][66][67][68] however, other studies were not able to replicate these findings. [69][70][71][72][73][74] A meta-analysis did not find an association between the TaqI A1 allele and smoking initiation, smoking persistence, cigarette consumption or cessation.…”

Section: Mk Ho and Rf Tyndale 86mentioning

confidence: 99%

Overview of the pharmacogenomics of cigarette smoking

Tyndale

2007

Pharmacogenomics J

102

View full text Add to dashboard Cite

Cigarette smoking increases the risk of numerous health problems, including cancer, cardiovascular and pulmonary disorders, making smoking the leading cause of preventable death in the world. Nicotine is primarily responsible for the highly addictive properties of cigarettes. Although the majority of smokers express a desire to quit, few are successful in doing so. Twin and family studies have indicated substantial genetic contributions to smoking behaviors. One major research focus has been to elucidate the specific genes involved; this has been accomplished primarily through genome-wide linkage analyses and candidate gene association studies. Much attention has focused on genes involved in the neurotransmitter pathways for the brain reward system and genes altering nicotine metabolism. This paper reviews the current state of knowledge for genetic factors implicated in smoking behaviors, and examines how genetic variations may affect therapeutic outcomes for drugs used to assist smoking cessation.

show abstract

D2 dopamine receptor gene (DRD2) Taql A polymorphism: reduced dopamine D2 receptor binding in the human striatum associated with the A1 allele

Cited by 522 publications

References 0 publications

Association of the DRD2 gene Taq1A polymorphism and smoking behavior: A meta-analysis and new data

Association of the DRD2 gene Taq1A polymorphism and smoking behavior: A meta-analysis and new data

Dopamine D2 receptor gene polymorphisms and response to cabergoline therapy in patients with prolactin-secreting pituitary adenomas

Overview of the pharmacogenomics of cigarette smoking

Contact Info

Product

Resources

About