Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “DRD2”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 325 records · Page 18Linked to original sources
PubMed1995

Dopamine D2 receptor gene variants: association and linkage studies in impulsive-addictive-compulsive behaviour.

Drug and alcohol seeking behaviour has become a great global problem affecting millions of inhabitants with a cost to society in the billions. Dopaminergic reward pathways have frequently been implicated in the etiology of addictive behaviour. While other neurotransmitters have also been implicated, to date the only molecular genetic defect which has been found to associate with alcoholism, drug dependency, obesity, smoking, pathological gambling, attention-deficit-hyperactivity disorder (ADHD), Tourette syndrome, as well as other related compulsive behaviours, are the variants of the dopamine D2 receptor gene (DRD2). In this review of the available data on the subject, we report a number of independent meta-analyses that confirm an association of DRD2 polymorphisms and impulsive-additive-compulsive behaviour (IACB), which we have termed "Reward Deficiency Syndrome". While we agree that Meta-analyses of all exant studies support an association of variants of DRD2 and IACB, correct negative findings with alcoholism may be due to differences in assessing controls and inclusion/exclusion criteria for selection of diseased probands.

Behavior, Addictive↗
PubMed2000

Association study of dopamine receptor gene polymorphisms with drug-induced hallucinations in patients with idiopathic Parkinson's disease.

Some patients with idiopathic Parkinson's disease experience hallucinations as a result of treatment with levodopa and dopamine agonists. There is evidence for some heterogeneity in these hallucinating patients based on duration of Parkinson's disease at onset of hallucinations. We compared the frequency of polymorphisms in the dopamine D2 and D3 receptor genes between patients with drug-induced hallucinations and non-hallucinating patients. Two polymorphisms close to DRD2 and one in DRD3 were studied. No association was found with the whole group of hallucinating patients and their controls. However, an association was found with late-onset hallucinations and the C allele of the TaqIA polymorphism, 10.5 kb 3' to DRD2. This polymorphism may be in linkage disequilibrium with a mutation in DRD2 or a nearby gene that predisposes to drug-induced hallucinations which occur later in the course of idiopathic Parkinson's disease.

Alleles↗
PubMed2001

The -141C Ins/Del polymorphism of the dopamine D2 receptor gene is not associated with either migraine or Parkinson's disease.

Abnormalities in dopamine neurotransmission at the dopamine D2 receptor (DRD2) have been implicated in both migraine and Parkinson's disease. Positive associations have also been found between polymorphisms within the DRD2 gene and both of these conditions. The -141C Ins/Del polymorphism in the DRD2 receptor gene is a putative functional polymorphism. The purpose of this study was to determine whether it and any genes in linkage disequilibrium with this marker are involved in either of these conditions. We have compared the genotype and allele frequencies of the -141C Ins/Del polymorphism in 200 migraineurs and 260 Parkinson's disease cases with 464 controls. We have found no association between the receptor gene and either condition (P = 0.89 and P = 0.56 respectively). Our findings do not support the hypothesis that this polymorphism is involved in the aetiology of migraine or Parkinson's disease.

Adolescent↗
PubMed2001

Association analysis for dopamine D2 receptor Taq1 polymorphism with P300 event-related potential for normal young females.

P300 has been demonstrated abnormal for a variety of neuropsychiatric disorders, and heritability has been proposed. We analyzed the event-related potentials for three DRD2 genotype groups in 134 normal young females. The results demonstrate that there is no association for DRD2 genotype and P300 components. Our negative findings in normal subjects suggest association demonstrated for P300 latency and the DRD2 allele may be disease dependent.

Adult↗
PubMed2001

Genetic polymorphisms of the promoter region of dopamine D2 receptor and dopamine transporter genes and alcoholism among four aboriginal groups and Han Chinese in Taiwan.

This study aims to examine the relationship between the functional polymorphism at the promoter region of the dopamine D2 receptor (DRD2) gene (i.e. -141C Ins/Del) and variable number of tandem repeat polymorphism at the 3' untranslated region of the dopamine transporter (DAT) gene (SLC6A3) with alcoholism in a case-control study. The cases (n = 203) were alcohol dependents with withdrawal symptoms, and the controls (n = 213) were sex- and ethnicity-matched individuals who were screened to exclude those with alcohol problems among four aboriginal groups (Atayal, Ami, Bunun, and Paiwan) and Han Chinese in Taiwan. To control for potential confounding factors, we excluded tobacco abusers from control subjects in part of the analysis and compared the distribution of the genetic polymorphisms in alcoholics with severe medical complications versus those with less severe medical complications. There were no differences in allele and genotype frequencies of these two distinct genetic markers between alcoholics and control subjects in these five different ethnic groups. There was no significant linkage disequilibrium between the -141C polymorphism and two other DRD2 polymorphisms (TaqI A and NcoI). The results remained unchanged when cases were limited to alcoholics with more severe medical complications or when tobacco abusers were excluded from control subjects. The results suggest that both the DRD2 promoter region and the DAT gene do not play a significant role in conferring vulnerability to alcoholism.

Adult↗
PubMed2002

No association for D2 and D4 dopamine receptor polymorphisms and methamphetamine abuse in Chinese males.

The D2 and D4 dopamine receptors (DRD2 and DRD4) play major roles in the central effects of psychostimulants and in the reward system. Previous studies, although not all, have demonstrated associations between the DRD2 TaqI and the DRD4 exon III variable number tandem repeat (VNTR) polymorphisms and substance dependence. For this study, we have investigated the associations between these two polymorphisms and methamphetamine (MAP) dependence, as manifested in a Chinese-male sample population. No significant difference was demonstrated for genotype or allele frequency when comparing MAP-dependent and control cases for the DRD2 TaqI and the DRD4 gene exon III VNTR polymorphisms, suggesting that these two polymorphisms do not play major roles in MAP dependence for our sample of Chinese males.

Amphetamine-Related Disorders↗
PubMed2006

Risk factors for extrapyramidal symptoms during treatment with selective serotonin reuptake inhibitors, including cytochrome P-450 enzyme, and serotonin and dopamine transporter and receptor polymorphisms.

INTRODUCTION: Extrapyramidal symptoms (EPS) are rare adverse drug reactions to selective serotonin reuptake inhibitors (SSRIs). This study aimed to investigate the potential risk factors for EPS associated with SSRIs including polymorphisms of cytochrome P-450 isoenzymes, and serotonin and dopamine transporters and receptors. METHODS: All spontaneous adverse drug reaction reports received by the Swedish Medical Products Agency until December 1999 that were coded with EPS and judged to be at least possibly related to SSRI treatment were included in the study. Reporting physicians received a form for collection of relevant information including current and previous use of SSRIs and antipsychotics, alcohol or substance abuse, central nervous system damage, a history of epilepsy or EPS, and a family history of Parkinson disease. A blood sample was also requested for genotyping of selected cytochrome P-450, and serotonin and dopamine transporter and receptor mutations. RESULTS: A total of 64 cases of EPS were reported. Twenty-eight forms (46%) were returned, and 20 blood samples were obtained. Identified potential risk factors included age of 65 years or older and the presence of the A1 allele of the D2 dopamine receptor gene (DRD2) Taq1A polymorphism (relative risk, 2.4; 95% confidence interval, 1.2-4.5 vs literature controls). No relationship was apparent for sex, drug dose, or other genetic polymorphisms. At least 1 additional potential risk factor for EPS, such as a history of central nervous system damage, alcohol or substance abuse, epilepsy, Parkinson disease, previous or current exposure to antipsychotic drugs, concomitant treatment with other antidopaminergic or serotonergic agents, or a history of EPS, was found in 93% of the cases. CONCLUSION: The risk of EPS with SSRIs seems to increase with advanced age and with the presence of the A1 allele of DRD2 Taq1A polymorphism. Because of the small sample size of our study and the use of historical controls rather than patients who did not experience EPS during SSRIs treatment, the DRD2 finding is preliminary and needs to be replicated in other studies before firm conclusions can be drawn. At least 1 additional potential risk factor was found in almost all cases.

Adult↗
PubMed2005

The A1 allele of the human D2 dopamine receptor gene is associated with increased activity of striatal L-amino acid decarboxylase in healthy subjects.

The A1 allele of the TaqI restriction fragment length polymorphism (RFLP) of the human dopamine D2 receptor gene (DRD2) is associated with a low density of D2 dopamine receptors in the striatum. Because of the important role of D2 autoreceptors in regulating dopamine synthesis, we aimed to examine whether subjects with the A1 allele have altered presynaptic dopamine function in the brain. We also studied the effects of two other DRD2 polymorphisms, C957 T and--141C Ins/Del, which have been suggested to affect D2 receptor levels in brain. The relationships between the TaqIA RFLP, C957 T and--141C Ins/Del polymorphisms and striatal dopamine synthesis in 33 healthy Finnish volunteers were studied using positron emission tomography and [18F]fluorodopa ([18F]FDOPA), a radiolabelled analog of the dopamine precursor L-DOPA. Heterozygous carriers of the A1 allele (A1/A2; 10 subjects) had significantly higher (18%) [18F]FDOPA uptake in the putamen than subjects without the A1 allele (A2/A2; 23 subjects). C957 T and--141C Ins/Del polymorphisms did not significantly affect [18F]FDOPA Ki values. These results demonstrate that the A1 allele of DRD2 gene is associated with increased striatal activity of aromatic L-amino acid decarboxylase, the final enzyme in the biosynthesis of dopamine and the rate-limiting enzyme for trace amine (e.g. beta-phenylethylamine) synthesis. The finding can be explained by lower D2 receptor expression leading to decreased autoreceptor function, and suggests that dopamine and/or trace amine synthesis rate is increased in the brains of A1 allele carriers.

Alleles↗
PubMed1997

An association study between the Cys311 variant of dopamine D2 receptor gene and schizophrenia in the Okinawan population.

Neuroleptic drugs have a high affinity for the dopamine D2 receptor (DRD2); therefore DRD2 is thought to be a candidate gene for schizophrenia. Arinami et al. have reported a positive association between schizophrenia and the Cys311 variant of the DRD2 gene. We determined the allele frequency of this polymorphism in 78 Okinawan schizophrenic patients and 112 control subjects. The patients and controls did not differ significantly in allele frequencies of Cys311.

Adolescent↗
PubMed2007

Signatures of positive selection in genes associated with human skin pigmentation as revealed from analyses of single nucleotide polymorphisms.

Phenotypic variation between human populations in skin pigmentation correlates with latitude at the continental level. A large number of hypotheses involving genetic adaptation have been proposed to explain human variation in skin colour, but only limited genetic evidence for positive selection has been presented. To shed light on the evolutionary genetic history of human variation in skin colour we inspected 118 genes associated with skin pigmentation in the Perlegen dataset, studying single nucleotide polymorphisms (SNPs), and analyzed 55 genes in detail. We identified eight genes that are associated with the melanin pathway (SLC45A2, OCA2, TYRP1, DCT, KITLG, EGFR, DRD2 and PPARD) and presented significant differences in genetic variation between Europeans, Africans and Asians. In six of these genes we detected, by means of the EHH test, variability patterns that are compatible with the hypothesis of local positive selection in Europeans (OCA2, TYRP1 and KITLG) and in Asians (OCA2, DCT, KITLG, EGFR and DRD2), whereas signals were scarce in Africans (DCT, EGFR and DRD2). Furthermore, a statistically significant correlation between genotypic variation in four pigmentation candidate genes and phenotypic variation of skin colour in 51 worldwide human populations was revealed. Overall, our data also suggest that light skin colour is the derived state and is of independent origin in Europeans and Asians, whereas dark skin color seems of unique origin, reflecting the ancestral state in humans.

Asian People↗
PubMed1996

Lack of allelic association of dopamine D1 and D2 (TaqIA) receptor gene polymorphisms with reduced dopaminergic sensitivity to alcoholism.

Our study tested the hypothesis of whether the sensitivity of central dopamine receptors corresponds to the genotypic constitution of DNA-polymorphisms of the dopamine D1 and D2 receptor (DRD1, DRD2) genes and is associated with poor treatment outcome. Therefore, 97 alcohol-dependent patients were assessed according to their sensitivity of central dopamine receptors (apomorphine-induced secretion of growth hormone), clinical outcome during a 6-month observation period, and genotypic constitution of the TaqIA restriction fragment length polymorphism (RFLP) at the DRD2 locus and of the Bsp1286I RFLP at the DRD1 locus. On the 1st day of detoxification, dopamine receptor hyposensitivity was found in treatment nonresponders, but not in responders. Apomorphine-induced growth hormone release did not differ significantly in alcoholics with different genotypes of the DRD1 and DRD2 RFLPs. Neither did we find a significant allelic association with treatment response. Thus, we did not find evidence for a genetic determination of dopamine receptor hyposensitivity in alcoholics with poor treatment outcome.

Adult↗
PubMed2002

Dopamine D2 receptor and N-methyl-D-aspartate receptor 2B subunit genetic variants and intelligence.

The dopaminergic and glutamate systems have been implicated in cognitive function. We tested the associations between the dopamine D2 receptor (DRD2) and N-methyl-D-aspartate receptor 2B subunit (GRIN2B) gene variants and intelligence quotient (IQ). Subjects with the DRD2 A1/A1 genotype had a significantly higher mean performance IQ than A2/A2 carriers, while no significant differences in IQ scores were determined for the three GRIN2B genotype groups. These results suggest that genetic variants of the DRD2 gene may play a role in cognitive function. Considering the major role played by the dopaminergic system in general cognitive function, genetic variants of the dopamine receptors and those involved in metabolism and modulation of reuptake should be tested to improve gene-based prediction of general cognitive function.

Adult↗
PubMed2004

Interacting effects of genetic predisposition and depression on adolescent smoking progression.

OBJECTIVE: The goal of the present study was to identify specific genetic associations with smoking progression in adolescents and to determine whether these genetic effects on smoking practices are potentiated by depression symptoms. METHOD: Effects of dopamine transporter (SLC6A3) and dopamine receptor (DRD2) genetic variants on smoking progression were evaluated in a cohort of 615 adolescents, including those who had never smoked, and in a subgroup including only adolescents who had been exposed to nicotine (i.e., smoked at least a puff of a cigarette) (N=292). These adolescents were followed from 9th to 11th grade. Depression symptoms were also assessed. RESULTS: In the model of adolescents with a previous smoking experience, the likelihood of progressing to a higher level of smoking by the 11th grade increased almost twofold with each additional DRD2 A1 allele. The likelihood of smoking progression with each additional A1 allele was more pronounced among adolescents with substantial depression symptoms. The model including never-smokers revealed no significant genetic effects. Neither model revealed effects of SLC6A3. CONCLUSIONS: These results provide the first evidence, to the authors' knowledge, for an association of the DRD2 A1 allele with smoking progression among adolescents. This effect is potentiated by depression symptoms. These effects appear to be specific to adolescents who have had at least some nicotine exposure (i.e., at least a puff of a cigarette).

Adolescent↗
PubMed2005

Genetics and epigenetics in major psychiatric disorders: dilemmas, achievements, applications, and future scope.

No specific gene has been identified for any major psychiatric disorder, including schizophrenia, in spite of strong evidence supporting a genetic basis for these complex and devastating disorders. There are several likely reasons for this failure, ranging from poor study design with low statistical power to genetic mechanisms such as polygenic inheritance, epigenetic interactions, and pleiotropy. Most study designs currently in use are inadequate to uncover these mechanisms. However, to date, genetic studies have provided some valuable insight into the causes and potential therapies for psychiatric disorders. There is a growing body of evidence suggesting that the understanding of the genetic etiology of psychiatric illnesses, including schizophrenia, will be more successful with integrative approaches considering both genetic and epigenetic factors. For example, several genes including those encoding dopamine receptors (DRD2, DRD3, and DRD4), serotonin receptor 2A (HTR2A) and catechol-O-methyltransferase (COMT) have been implicated in the etiology of schizophrenia and related disorders through meta-analyses and large, multicenter studies. There is also growing evidence for the role of DRD1, NMDA receptor genes (GRIN1, GRIN2A, GRIN2B), brain-derived neurotrophic factor (BDNF), and dopamine transporter (SLC6A3) in both schizophrenia and bipolar disorder. Recent studies have indicated that epigenetic modification of reelin (RELN), BDNF, and the DRD2 promoters confer susceptibility to clinical psychiatric conditions. Pharmacologic therapy of psychiatric disorders will likely be more effective once the molecular pathogenesis is known. For example, the hypoactive alleles of DRD2 and the hyperactive alleles of COMT, which degrade the dopamine in the synaptic cleft, are associated with schizophrenia. It is likely that insufficient dopaminergic transmission in the frontal lobe plays a role in the development of negative symptoms associated with this disorder. Antipsychotic therapies with a partial dopamine D2 receptor agonist effect may be a plausible alternative to current therapies, and would be effective in symptom reduction in psychotic individuals. It is also possible that therapies employing dopamine D1/D2 receptor agonists or COMT inhibitors will be beneficial for patients with negative symptoms in schizophrenia and bipolar disorder. The complex etiology of schizophrenia, and other psychiatric disorders, warrants the consideration of both genetic and epigenetic systems and the careful design of experiments to illumine the genetic mechanisms conferring liability for these disorders and the benefit of existing and new therapies.

Brain↗
PubMed2001

A Ser311Cys mutation in the human dopamine receptor D2 gene is associated with reduced energy expenditure.

Brain dopaminergic pathways play a major role in the control of movement. Absence of the murine dopamine D2 receptor gene (drd2) produces bradykinesia and hypothermia. A Ser311Cys mutation of the human DRD2 produces a marked functional impairment of the receptor and is associated with higher BMI in some populations. We hypothesized that the Ser311Cys mutation of DRD2 may inhibit energy expenditure. Here we report that total energy expenditure (doubly labeled water) measured in 89 nondiabetic Pima Indians was 244 kcal/ day lower in homozygotes for the Cys311-encoding allele when compared with those heterozygous and homozygous for the Ser311-encoding allele (P = 0.056). The 24-h resting energy expenditure (respiratory chamber) measured in 320 nondiabetic Pimas was also 87 kcal/day lower in homozygotes for the Cys311-encoding allele when compared with those heterozygous and homozygous for the Ser311-encoding allele (P = 0.026). These findings are the first evidence that a genetic mutation is associated with reduced energy expenditure in humans. Because the impact of this mutation on human obesity is small, we suggest that either the energy deficit induced is not large enough to significantly influence body weight in this population and/or that the Cys311-encoding allele is also associated with reduced energy intake.

Adult↗
PubMed1999

Association of a functional mu-opioid receptor allele (+118A) with alcohol dependency.

Genetic association studies have implicated the TaqI A1 allele of the human dopamine D2 receptor gene (DRD2) as a risk-determining factor for alcohol dependency. However, as alcoholism is a disease of polygenic inheritance, the percentage of overall disease variance explained by the TaqI A1 allele is small. In searching for other genetic loci that may, either alone or in combination with DRD2, enhance prediction of alcoholism, we have found a novel association between a functional coding variant (+118A) within the human mu-opioid receptor gene and alcohol dependency. However, no association was detected between the DRD2 TaqI A1 allele and alcoholism in our sample nor did we find synergy between +118A and TaqI A1 alleles on prediction of risk for the disease. These results suggest that, at the molecular level, the endogenous mu-opioid receptor system is a contributing factor to the etiology of alcoholism.

Adult↗
PubMed2000

Dopamine receptor gene polymorphisms in Guangzhou Hans.

OBJECTIVE: To determine the distribution of dopamine D2, D3, and D5 receptor(DRD2, DRD3, DRD5) gene polymorphisms in Guangzhou Hans. METHODS: A total of 141 healthy Guangzhou Hans were studied by the use of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and PCR-amplification of specific allele (PASA) techniques. Current results were compared with the data on other ethnic groups. RESULTS: Within the 141 individuals tested, the frequencies of the A1(Taq I-) and A2(Taq I+) alleles of the TaqI A mutation site in the 3'non-coding region of the DRD2 gene were found to be 48% and 52%, respectively. The observed frequencies of the A1A1, A1A2 and A2A2 genotypes were found to be 17%, 52% and 31%, respectively, which met Hardy-Weinberg equilibrium. The frequencies of the A1 and A2 alleles of the Bal I mutation site in the exon 1 of DRD3 gene were found to be 73% and 27%, respectively. The observed frequencies of the A1A1, A1A2 and A2A2 genotypes were found to be 53%, 39% and 8%, respectively, which met Hardy-Weinberg equilibrium. The frequencies of the 1 and 2 alleles of the Msp I mutation site in the intron 5 of DRD3 gene were found to be 62.5% and 37.5%, respectively. The observed frequencies of the 1-1, 1-2 and 2-2 genotypes were found to be 35%, 55% and 10%, respectively, which met Hardy-Weinberg equilibrium. No linkage disequilibrium was observed between the Bal I and Msp I polymorphism in Guangzhou Hans(chi(2)=0165, P>0.05). The frequencies of the T and C alleles of the T978C mutation site of DRD5 gene were found to be 51% and 49%, respectively. The observed frequencies of the T/T, T/C and C/C genotypes were found to be 23.6%, 54.6% and 21.8%, respectively, which met Hardy-Weinberg equilibrium. CONCLUSION: The polymorphisms of DRD2, DRD3, DRD5 gene in Guangzhou Hans were high and different from those in other populations.

Adult↗
PubMed2003

No association of antipsychotic agent-induced weight gain with a DA receptor gene polymorphism and therapeutic response.

AIM: To investigate whether there is an association of antipsychotic agent-induced weight gain with the TaqI A polymorphism of dopamine D2 receptor (DRD2) gene and therapeutic response to antipsychotic treatment in schizophrenia. METHODS: Genotyping was performed using the PCR-RFLP techniques in a total of 117 first-episode Chinese Han schizophrenic patients (mean age 26+/-8 a; 58 male, 59 female). Moreover, the measurements were finished either for baseline weight and body mass index (BMI) or for changed weight and BMI 10 weeks after antipsychotic treatment. The Positive and Negative Symptom Scale (PANSS) was used for the evaluation of the improvement of clinical psychotic symptoms. RESULTS: There was an average increase in body weight of (3+/-3) kg or (6+/-6) % of baseline weight with a changed range of -7 kg - 12 kg or -7.8 % - 32.4 % 10 weeks after treatment, and the change in the BMI was associated with the baseline BMI and patients' age (P=0.0001; P=0.03; respectively). However, there was no significant difference in distribution of allelic frequencies (X2=0.65, v1, P>0.05) and genotype (x2=1.47, v2, P>0.05) between the subgroups, and the change in BMI was not associated with genotypes of DRD2. Furthermore, there was no relationship of the therapeutic response to antipsychotic treatment with changed BMI in the patients (P>0.05). CONCLUSION: The TaqI A polymorphism of DRD2 gene is therefore unlikely to play an important role in antipsychotic agent-induced weight gain, a side effect of antipsychotic treatment. Furthermore, increase in body weight is unlikely to be prediction of therapeutic response to antipsychotic treatment in schizophrenia.

Adult↗