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 397 records · Page 22Linked to original sources
PubMed2006

Clinical and genetic characteristics of Korean male alcoholics with and without attention deficit hyperactivity disorder.

AIMS: To examine the clinical and genetic characteristics of Korean male alcoholics with and without attention deficit hyperactivity disorder (ADHD). METHODS: The present study included 85 male alcoholics who were diagnosed as having DSM-IV alcohol dependence. A total of 28 (32.9%) alcoholics were diagnosed as having DSM-IV ADHD with ongoing symptoms in adulthood. For the evaluation of their psychiatric conditions, the alcohol dependence scale (ADS), Beck depression inventory (BDI), Beck anxiety inventory (BAI), Barratt impulsiveness scale (BIS), brief anger-aggression questionnaire (BAQ), overt aggression scale (OAS), codependence test, and obsessive compulsive drinking scale (OCDS) were administered. The genotype frequencies of the dopamine type 2 receptor gene (DRD2), aldehyde dehydrogenase type 2 gene (ALDH2), functional polymorphism in the regulatory region of the serotonin transporter gene (5-HTTLPR), and catechol-O-methyltransferase gene (COMT) polymorphisms were examined. RESULTS: Compared with alcoholics without ADHD, the mean ages for the onset of pathological drinking and alcohol withdrawal hallucinations were significantly earlier in alcoholics with ADHD. There was also a significant difference in the history of antisocial behaviour between the two groups. Compared with alcoholics without ADHD, the mean scores of the ADS, BDI, BAI, OAS, and OCDS were significantly higher in alcoholics with ADHD. With regard to the codependence test results, the mean scores of the interpersonal problem, low self-esteem and anxiety/fear subscales, and the mean total score of the codependence test were significantly higher in alcoholics with ADHD when compared with those without ADHD. There were no significant differences in the genotype frequencies of the DRD2, ALDH2, 5-HTTLPR, and COMT polymorphisms between alcoholics with and without ADHD. CONCLUSIONS: The results of this study suggest that the comorbidity of alcohol dependence and ADHD in this Korean sample forms a distinct clinical phenotype that shows an increased severity of alcohol-related symptoms and behavioural/emotional problems and that ADHD is associated with an increased risk for the early onset of alcohol dependence in Korean male alcoholics.

Adult↗
PubMed1992

Ataxia-telangiectasia: linkage analysis of chromosome 11q22-23 markers in Turkish families.

To further pinpoint the location of the genes for ataxia-telangiectasia on the long arm of chromosome 11, we performed linkage analysis and analysis of recombinants of genetic haplotypes on 14 Turkish families with ataxia-telangiectasia, 12 of which were consanguineous. These studies used more than 25 polymorphic genetic markers spanning a region of the long arm of chromosome 11 that is larger than 50 cM. Seven markers gave significant LOD scores to AT: CJ5, DRD2, CJ208, S144, CD3E, PBGD, and S147, as did haplotypes created with pairs of markers DRD2/CJ5 and S144/CJ208, giving recombination fractions (theta) of 0.00, 0.00, 0.05, 0.08, 0.03, 0.09, 0.07, 0.00, and 0.06, respectively. Monte Carlo analysis of these 14 Turkish families indicated the best location for a single AT gene to be within a 6 cM sex-averaged (3 cM male-specific) interval defined by STMY and CJ77; this was three times more likely than the next most likely location (peak III) at the DRD2 locus. The analysis also revealed a peak (peak II) between S147 and S133, which may represent the complementation group D gene. Recombinant analysis of haplotypes also localized an AT locus to the STMY-CJ77 interval. Taken together, these results suggest that at least two distinct AT loci exist (ATA and ATD) at 11q22-23, with perhaps a third locus, ATC, located very near to the ATA gene. This genetic heterogeneity further complicates plans to isolate the major ATA and ATC genes and to begin identifying AT carriers in the general population.

Ataxia Telangiectasia↗
PubMed2005

Sexually dimorphic link between dopamine D2 receptor gene and neuroticism-anxiety.

Prior theory-driven research probing the association between dopaminergic candidate genes and human personality has focused on the trait of novelty seeking. Here, we examined the association between the dopamine D2 receptor (DRD2) TaqI A polymorphism and two other personality traits, neuroticism-anxiety and agentic extraversion. We found no significant associations for agentic extraversion. However, for men, but not for women, we observed a strong and specific association between low neuroticism-anxiety and the A1+ allele of the DRD2 TaqI A polymorphism across two independent samples and across two alternative personality scales. We conclude that new theoretical models are needed to account for these and other recent reports of associations between neuroticism-anxiety and brain dopamine, which cannot be interpreted within the traditional framework.

Adult↗
PubMed1996

A study of the dopamine D2 receptor gene in pathological gambling.

Pathological gambling has been termed both the 'pure' and the 'hidden' addiction. 'Pure' because it is not associated with the intake of any addicting substance, and 'hidden' because it is an extension of a common, socially accepted behaviour. The Taq A1 variant of the human DRD2 gene has been associated with drug addiction, some forms of severe alcoholism, and other impulsive, addictive behaviours. We have sought to determine if there is a similar association with pathological gambling. A total of 222 non-Hispanic Caucasian pathological gamblers from multiple sites across the US participated in the study. Of these 171 donated a sample of blood, 127 filled out several questionnaires, and 102 did both. Of the 171 pathological gamblers 50.9% carried the D2A1 allele versus 25.9% of the 714 known non-Hispanic Caucasian controls screened to exclude drug and alcohol abuse, p < 0.00000001, odds ratio (OR) = 2.96. For the 102 gamblers who filled out the questionnaires, 63.8% of those in the upper half of the Pathological Gambling Score (more severe) carried the D2A1 allele (OR versus controls = 5.03), compared to 40.9% in the lower half (less severe). Of those who had no comorbid substance abuse, 44.1% carried the D2A1 allele, compared to 60.5% of those who had comorbid substance abuse. Forty-eight controls and 102 gamblers completed a shorter version of the Pathological Gambling Score. Of the 45 controls with a score of zero, 17.8% carried the D2A1 allele. Of the 99 gamblers with a score of 5 or more, 52.5% carried the D2A1 allele (chi 2 = 15.36, p = 0.00009). These results suggest that genetic variants at the DRD2 gene play a role in pathological gambling, and support the concept that variants of this gene are a risk factor for impulsive and addictive behaviours.

Adult↗
PubMed1996

A linkage study between bipolar disorder and genes involved in dopaminergic and GABAergic neurotransmission.

Neurobiological studies indicate a dysregulation of the dopaminergic and GABAergic neurotransmission in bipolar disorder. We examined two large families segregating bipolar disorder, for linkage with the genes encoding dopamine beta-hydroxylase, the dopamine transporter DAT1, the dopamine D2, D3 and D5 receptors, and the alpha-1, alpha-5 and beta-1 subunits of the GABAA receptor. Under at least one diagnostic model one of the two families provided evidence to exclude linkage for the DAT1, DRD2, DRD3, DRD5, DBH, GABRA1 and GABARB1 genes but could not exclude the GABRA5 locus. A second family excluded only the GABRA1 and GABRA5 loci at zero recombination and could not formally reject linkage at the DBH, DRD2, DRD3, DRD5, DAT1 and GABARB1 loci. Further analyses at these loci are warranted.

Bipolar Disorder↗
PubMed2002

No association between the dopamine D3 receptor gene and Korean alcohol dependence.

The genes encoding dopamine receptor (DR) subtypes have received considerable attention for the past several years as a potential candidate that may affect susceptibility to addictive disorder, including alcoholism. The many association studies that compared the frequencies of alleles of the dopamine D2 receptor (DRD2) gene between alcoholics and control groups have produced results, but some have been equivocal. Dopamine D3 receptor genes (DRD3) are in the same class as DRD2 but with different pharmacological properties. So we compared the distribution of genotypes and frequencies of BalI polymorphism of the DRD3 gene in alcoholics and controls to assess the role of the DRD3 gene in Korean alcoholism. For this study, 67 male probands from alcoholics and 67 age-matched normal male controls were engaged. No evidence for an allelic association was found between the A1 allele of DRD3 and alcoholism in a Korean population. These results suggest that any role played by this receptor may account for only part of the variation in susceptibility to alcoholism.

Adult↗
PubMed2005

Polymorphic variations in GSTM1, GSTT1, PgP, CYP2D6, CYP3A5, and dopamine D2 and D3 receptors and their association with tardive dyskinesia in severe mental illness.

This study tested the association between tardive dyskinesia (TD) and polymorphic variations in (a) 2 cytochrome P450 (CYP) genes (CYP2D6 or CYP3A5), (b) 2 DRD2 variants (Ser311Cys and -141C Ins/del) and the Ser9Gly DRD3 variants, (c) 2 glutathione S-transferases (GSTT1 and GSTM1), and (d) variations in the PgP gene, MDR1. The study sample included 516 severely mentally ill patients from Central Kentucky facilities. Logistic regression models that included clinical variables associated with TD were developed. Gene variants were added to these clinical models. The total sample included 31% (162/516) with TD where 30% (49/162) of those had severe TD. Polymorphisms in DRD2, MDR1, and GSTT1 were never significant. Two gene variants appeared to be significant after adding them to the clinical regression models: (1) Ser9Gly DRD3 polymorphism was associated with severe TD (odds ratio for patients with 1 mutant allele when compared with individuals with 2 wild types was 2.5, 95% confidence interval 1.1-5.6, whereas the odds ratio for patients with 2 mutant alleles when compared with individuals with 1 mutant was 2.8, 95% confidence interval 1.0-7.4), and (2) GSTM1 absence was associated with TD (odds ratio 1.7, 95% confidence interval 1.2-2.4) particularly in white women. The CYP2D6 and CYP3A5 absence showed potential for significant associations in larger samples, particularly in white men. New studies need to replicate whether these or other genes could be used conjointly with clinical variables to identify subjects at risk for TD in clinical settings.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2004

Progress in searching for susceptibility loci and genes for smoking-related behaviour.

Smoking behaviour is influenced by both genetic and environmental factors. Many years of twin and adoption studies have demonstrated that heritability is at least 50% responsible for both smoking initiation and smoking persistence. Furthermore, the extent, to which genetic and environmental factors contribute to smoking behaviour, is significantly different in men and women. Linkage analyses from several independent studies provide evidences for suggested linkage of smoking behaviour to chromosomes 1, 2, 4, 5, 6, 9, 10, 11, 14, 17, 18 and 21. However, almost none of these loci have been replicated yet. Furthermore, numerous population-based association studies have been performed to examine the effects of a number of candidate genes, such as cytochrome P450, dopamine receptor (DR) and transporter, serotonin transporter and nicotinic acetylcholine receptor, on smoking behaviour. However, many of these reports have not yet received independent confirmation. Of these candidate genes, the D2 dopamine receptor (DRD2) gene has been extensively studied. Meta-analysis of 12 reported studies showed a significantly higher prevalence of the DRD2 TaqI A1 allele in smokers than that in non-smokers (p < 0.0001; pooled OR = 1.50; 95% CI = 1.33-1.70). For other candidate genes, insufficient published studies are available to allow a meta-analysis to be performed, or meta-analysis showed no significant difference between smokers and non-smokers. More studies are necessary to determine whether these genes play a significant role in smoking behaviour.

Chromosomes, Human↗
PubMed1995

Loss of heterozygosity on chromosome 11 q in breast cancer.

AIMS: Chromosome 11q23 seems to be a site of frequent mutation in cancer. It also contains loci such as ataxia telangiectasia with possible importance in the pathogenesis of breast tumours. The short arm of chromosome 11 has been studied extensively in breast cancer, but the long arm, in particular the distal part, has been studied less frequently. Cytogenetic analysis has shown possible involvement of chromosome 11q in breast tumours. Chromosome transfer experiments have also implicated chromosome 11q in breast cancer. A high frequency of mutations might therefore be expected to occur on chromosome 11q in breast cancers. METHODS: Using restriction fragment analysis, the primary tumours of 41 patients with breast cancer were screened for mutations at five loci on chromosome 11q (D11Z1, INT2, (FGF3), DRD2, NCAM, and D11S29). RESULTS: Allelic loss occurred at a high frequency (59%) at D11S29. At NCAM, novel alleles were frequently seen on autoradiographs. Relatively low frequencies of mutation were detected at the other loci. Allelic loss at D11S29 was associated with the presence of lymph node metastases, but this may be a chance association. CONCLUSIONS: The frequency of allelic loss at the DS11S29 locus is high. The significance of novel alleles at NCAM and their relation to allelic loss at D11S29 are unclear. The results presented here do not permit fine mapping of a region of allelic loss, but suggest that the region of greatest loss lies distal to DRD2. The results provide further evidence for the importance of gene(s) near 11q23 in the pathogenesis of breast cancer, and of tumours in general.

Breast Neoplasms↗
PubMed1996

Chromosome 11q in sporadic colorectal carcinoma: patterns of allele loss and their significance for tumorigenesis.

AIMS: To analyse the frequency of loss of heterozygosity (allele loss, LOH) in a large sample of colorectal carcinomas using highly informative markers along chromosome 11q. METHODS: One hundred paired samples of colorectal cancer and normal tissue were genotyped at six microsatellite markers on chromosome 11q (cen-D11S1313-D11S901-DRD2/NCAM-D11S29- D11S968-tel). The high levels of heterozygosity at these markers allow allele loss to be determined in about 80% of cases at any one locus. The frequency of replication errors (RERs, microsatellite instability) has also been determined. RESULTS: LOH was found at frequencies of 25% and 29% at the distal D11S968 (11qter) and D11S29 (11q23.3) loci, slightly above the accepted baseline of 0-20%. Allele loss at NCAM, DRD2, D11S901, and D11S1313 was not raised above baseline levels. The probable genetic mechanism of allele loss--chromosomal non-disjunction, mitotic recombination, deletion, or gene conversion--seemed to vary between tumours and no consistent mechanism of mutation was found. Microsatellite instability was found in 23 (23%) tumours. No associations were found between LOH and clinical data (patient sex, age at presentation, tumour site, and Duke's stage). CONCLUSIONS: Although gene(s) on 11q may have a role in the development of a minority of colorectal carcinomas, this study provides evidence against the general importance of allele loss on chromosome 11q in the pathogenesis of colorectal cancer. The results also have implications for the importance of 11q in other cancers: it seems less likely that a single tumour supressor gene at this location promotes the growth of all types of tumour when lost. Rather, one or more genes with tissue specific effects may be involved.

Age Factors↗
PubMed2004

Genetic heterogeneity in ten families with myoclonus-dystonia.

BACKGROUND: Myoclonus-dystonia (M-D) is a movement disorder with autosomal dominant inheritance and reduced penetrance but may also occur sporadically. Recently, mutations in the epsilon-sarcoglycan gene (SGCE) were shown to cause M-D. Furthermore, single variants in the dopamine D2 receptor (DRD2) and DYT1 genes were found in combination with SGCE mutations in two M-D families, and another M-D locus was recently mapped to chromosome 18p11 in one family. METHODS: The authors clinically and genetically characterised ten consecutive cases with myoclonus-dystonia; seven familial and three sporadic. Twenty nine M-D patients and 40 unaffected family members underwent a standardised clinical examination by a movement disorder specialist. Index cases were screened for mutations in the SGCE, DYT1, and DRD2 genes and for deletions of the SGCE gene. Suitable mutation negative families were tested for linkage to the SGCE region and to chromosome 18p11. RESULTS: Two SGCE mutations were detected among the seven familial but no mutation in the sporadic cases. Haplotype analysis at the new M-D locus was compatible with linkage in two families and excluded in another family, suggesting at least one additional M-D gene. There were no obvious clinical differences between M-D families with and without detected mutations. CONCLUSION: M-D is genetically heterogeneous with SGCE mutations accounting for the disease in only part of the clinically typical cases.

Adolescent↗
PubMed2000

Association studies of candidate genes in bipolar disorders.

The aim of the investigation was to test genes for predisposition to bipolar affective disorder. Therefore, we studied candidate genes in a sample of unrelated patients (n = 102) and healthy controls (n = 79) of Austrian origin, searching for a possible association between polymorphic DNA markers of 5 candidate genes (serotonin transporter, 5-HTT; serotonin 2a receptor, 5-HT2a; dopamine D2 receptor, DRD2; dopamine D3 receptor, DRD3; dopamine transporter, DAT1) and bipolar disorder. There was an association between allelic and genotypic frequencies of 5-HTT and affection status (p = 0.014 and p = 0.017, respectively). However, after correction for multiple comparisons (Bonferroni), these results did not remain significant. Nevertheless, the findings might suggest that alterations in the structure of 5-HTT are involved in the pathogenesis of bipolar disorder, which could have major implications in treatment. No association between 5-HT2a, DRD2, DRD3, DAT1 and bipolar disorder was found.

Adult↗
PubMed1994

A molecular investigation suggests no relationship between obsessive-compulsive disorder and the dopamine D2 receptor.

Some studies suggest a relationship between obsessive-compulsive disorder (OCD) and Gilles de la Tourette's syndrome. The pathophysiology of the latter may involve the dopamine system. We screened three important exons of the dopamine D2 receptor (DRD2) gene for mutations in a group of OCD patients with or without tics. No structural changes were found, suggesting no relationship between DRD2 and OCD. Moreover, the frequency of the polymorphism in exon 6 was different from that found in schizophrenics.

Adolescent↗
PubMed1994

Nonlinkage of bipolar illness to tyrosine hydroxylase, tyrosinase, and D2 and D4 dopamine receptor genes on chromosome 11.

OBJECTIVE: Previous linkage and allelic association studies using DNA polymorphisms, cosegregation of cytogenetic abnormalities with psychiatric illness, and assignment of genes involved in neutotransmitter metabolism suggested that chromosome 11 may harbor a gene predisposing to bipolar illness. The authors examined linkage in the families of 14 probands with bipolar illness, with the candidate genes tyrosine hydroxylase (TH), D4 dopamine receptor (DRD4) at 11p15, tyrosinase (TYR) at 11q14-q21, and D2 dopamine receptor (DRD2) at 11q22-q23, as well as with the c-Harvey-ras oncogene (HRAS) and insulin gene (INS), both located at 11p15, a region that previously showed linkage to bipolar illness. METHOD: The genetic data were analyzed with both lod score analysis (parametric) and affected-sib-pair analysis (nonparametric); both narrow and broad definitions of the clinical phenotype were used. Further influences of diagnostic uncertainties were accounted for by using diagnostic probability classes weighing the stability of each phenotype. RESULTS: Two-point linkage results excluded close linkage of bipolar illness to each candidate gene; negative results were also obtained when the narrow definition of the clinical phenotype was used. Moreover, multipoint linkage analysis of HRAS and INS excluded the 11p15 region encompassing both DRD4 and TH. In agreement with the negative linkage results, affected-sib-pair analysis did not show preferential sharing of marker alleles at any of the candidate genes. CONCLUSIONS: The negative results obtained under different genetic models exclude a frequent role for DRD4, TH, TYR, and DRD2 in the pathogenesis of bipolar illness.

Adolescent↗
PubMed2001

Association of short-term response to haloperidol treatment with a polymorphism in the dopamine D(2) receptor gene.

OBJECTIVE: Pharmacogenetic influences on therapeutic response to neuroleptic treatment are poorly understood. This study investigates the association of response to short-term haloperidol treatment with a Taq I polymorphism in the DRD2 gene. METHOD: Fifty-seven patients with acute psychosis were treated with haloperidol for up to 28 days. Improvement and response were measured by using the Positive and Negative Syndrome SCALE: Forty-one patients were homozygous for allele 2, and 16 were heterozygous. RESULTS: Heterozygous patients showed a greater improvement in positive, but not in negative, symptoms on all treatment days than patients homozygous for allele 2. Differences in improvement of positive symptoms reached statistical significance on days 14, 21, and 28. On treatment day 14, 10 (62.5%) of 16 heterozygous patients had at least 50% improvement of positive symptoms, compared with 11 (28.9%) of 38 homozygous patients. CONCLUSIONS: These results support the hypothesis that genetic variations in the DRD2 gene may influence the individual response to antipsychotics.

Adult↗
PubMed1994

The D2 dopamine receptor gene and alcoholism: a genetic effect in the liability for alcoholism.

Three of five recent association studies have demonstrated an increased frequency of the A1 allele of the TaqI Restriction Fragment Length Polymorphism (RFLP) of the DRD2 locus in alcoholics compared to controls. One of three family studies has shown preliminary results in favour of linkage of this locus with alcoholism and heavy drinking. The possible mechanism of a genetic effect of the DRD2 locus in alcoholism remains open to speculation, but many involve personality characteristics such as impulsiveness or spontaneity. The applications of the findings of research in this field offer much potential for the prevention and treatment of alcoholism, but also raise certain ethical issues when applied to screening programmes. Future research will be assisted by the development of new, and more informative, genetic markers which are now available at this locus.

Alcoholism↗
PubMed2004

Association studies of neurotransmitter gene polymorphisms in alcoholic Caucasians.

Ethanol enhances mesolimbic/cortical dopamine activity in reward and reinforcement circuits. We investigated the hypothesis that risk for alcoholism may be mediated by genes for neurotransmitters associated with the dopamine reward system as well as genes for enzymes involved in ethanol metabolism. DNA was extracted from brain tissue collected at autopsy from pathologically characterized alcoholics and controls. PCR-based assays showed that alcoholism was associated with polymorphisms of the dopamine D2 receptor (DRD2) TaqI B (P = .029) and the GABAA-beta2 subunit C1412T (P = .012) genes, but not with the glutamate receptor subunit gene NMDAR2B (366C/G), the serotonin transporter gene (5HTTL-PR), the dopamine transporter gene DAT1(SLC6A3), the dopamine D2 receptor gene DRD2 TaqI A, or the GABAA alpha1(A15G), alpha6(T1519C), and gamma2(G3145A) subunit genes. The glial glutamate transporter gene EAAT2 polymorphism G603A was associated with alcoholic cirrhosis (P = .048). The genotype for the most active alcohol dehydrogenase enzyme ADH1C was associated with a lower risk of alcoholism (P = .026) and was less prevalent in alcoholics with DRD2TaqIA2/A2 (P = .047), GABAA-beta2 1412C/C (P = .01), or EAAT2 603G/A (P = .022) genotypes. Combined DRD2TaqI A or B with GABAA-beta2 or EAAT2 G603A genotypes may have a concerted influence in the predisposition to alcoholism.

Alcoholism↗
PubMed2001

Association study of dopamine D2, D3 receptor gene polymorphisms with motor fluctuations in PD.

The authors investigated the association between dopamine receptor D2, D3 gene polymorphisms, and the risk of developing motor fluctuations in PD. DRD3 BalI and MspI polymorphisms were not associated with risk of developing motor fluctuations. However, the genotypic distribution of DRD2 TaqIA polymorphism was significantly different in motor fluctuators and nonmotor fluctuators. These findings suggest that DRD2 TaqIA polymorphism may be associated with an increased risk for developing motor fluctuations in PD.

Adult↗