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.

532 records · Page 30Linked to original sources

[Genetics of addictive disorders].

Given the spectacular advances of genetics during the last five years, it seems appropriate to revisit the important subject of genetics of alcoholism and substance abuse. In recent studies alcohol abuse was shown to have an hereditability of roughly 38%, whereas psychostimulant and opiate use exhibit hereditabilities of 11 to 45%. The hereditability of smoking was found to be around 50%. There is a strong comorbidity between alcoholism and smoking. More than 80% of alcoholics smoke cigarettes in the U.S.A. Other genetic methods such as linkage analysis, allele sharing methods, association studies and analysis of inbred, transgenic and gene-knockout rodents, have partially agreed in showing that the 5HT-1B serotonin receptor and the DRD1, DRD2 and DRD4 dopamine receptors, as well as the dopamine transporter DAT, play an important role in behaviors related to alcoholism and substance abuse. Some neurochemical markers, as for example monoamine oxidase and adenylate cyclase have also been implicated in addictive disorders. The aldehyde dehydrogenase allele ALDH2*2 has a protective effect against alcoholism. Two whole genome linkage studies have shown linkage to chromosomal regions that are in the proximity of the DRD4 dopamine receptor, the GABA receptor gene cluster and the alcohol dehydrogenase gene cluster.

Alcoholism↗

[Molecular genetic polymorphism of the genes of neurotransmitter systems in schizophrenics with early manifestation of the disease].

Molecular-genetic polymorphism of genes-candidates was investigated: the genes of serotonin receptor--type 2a (HTR2A), dopamine receptor gene--type 2, serotonin transporter (5HTTLPR). Thirty one schizophrenic patients whose age was 12.6 +/- 3.6 years at the onset of the disease and 208 patients whose age was 23.5 +/- 6.7 years at the onset of the disease were examined. The frequencies of HTTLPR and DRD2 genotypes differed insignificantly in both groups. The distribution of 5HTR2A genotypes in the schizophrenic group with an early manifestation of the disease differed from that with a later manifestation significantly (chi 2 = 6.27; df = 2; p = 0.044). The relative risk (odds ratios) was 7.9 with 95% significance interval 1.008-61.94; p = 0.045. The severity of the disease and a positive family history were also examined in A2A2 genotype carriers. A positive family history was found in 9 (52.9%) of the 17 schizophrenics with an early manifestation and only in 15 (21.1%) of 71 patients of the similar group with a later one. Assessment of the clinical symptoms revealed that the total scores by the negative symptomatology subscale (PANSS) was higher in the patients with an early manifestation than in those with later one; but these differences did not achieve the significance level. These and earlier findings lead to the conclusion that A2A2 genotype was more frequently observed in the patients with more pronounced negative symptoms and high hereditary burden, which suggests that the A2A2 genotype is associated with an early onset.

Adult↗

Gene-environment Interactions and Polymorphism Studies of Cancer Risk in the Hospital-based Epidemiologic Research Program at Aichi Cancer Center II (HERPACC-II).

Genetic polymorphisms may modify the effects of environmental risk factors on cancer occurrence. We have recently launched a comprehensive epidemiologic project, HERPACC II (Hospital-based Epidemiologic Research Program at Aichi Cancer Center II), including both lifestyle and polymorphism data, following HERPACC-I which solely concentrated on lifestyle data. As of April 2001, about 3000 samples of DNA are being stored to conduct case-control studies. Genotyping of 46 polymorphisms has been conducted at the laboratory of the Division of Epidemiology and Prevention. Twelve case-control studies and two papers on a new PCR method, PCR-CTPP (polymerase chain reaction with confronting two-pair primers), have been accepted for publication. Significant findings in Japanese were found for 1) gene-environment interaction for esophageal cancer between heavy drinking and aldehyde dehydrogenase 2 (ALDH2), 2) malignant lymphoma risk with methylenetetrahydrofalate reductase (MTHFR) and methionine synthase (MS), 3) interactions between smoking and two polymorphisms, interleukin 1B (IL-1B) and myeloperoxidase (MPO) for Helicobacter pylori infection, and 4) smoking habits with dopamine receptor D2 (DRD2) and IL-1B. Further studies on interactions with polymorphisms will continue to be conducted for Japanese, using larger sizes of samples.

Journal Article↗

[Molecular pharmacogenetic studies of drug responses to obsessive-compulsive disorder and six functional genes].

OBJECTIVE: To investigate the associations between the drug responses to obsessive -pulsive disorder (OCD) and six functional genes related with serotonin and dopamine. METHODS: One hundred and thirteen OCD nuclear families were collected. The OCD patients were treated with serotonin reuptake inhibitors (SRIs) for 8 weeks and the drug responses were assessed using the Yale-Brown obsessive-compulsive scale (Y-BOCS). The patients were divided into drug responders group and non-responders group according to the reducing rate of Y-BOCS score. The genotypes of six genes were determined with the Amp-FLP and Amp-RFLP techniques and analyzed by transmission disequilibrium test (TDT). The six genes are serotonin 2A receptor (5-HT2A), serotonin transporter (5-HTT), dopamine D2 receptor ( DRD2), dopamine D4 receptor (DRD4), catechol-O- methyltransferase (COMT) and monoamine oxidase A (MAOA). RESULTS: No association was found between the six genes and different drug responses groups. However, there was significant difference between the drug responders and non-responders in homozygosity at the 5-HT2A -1438G/A locus (chi(2)=4.69, P=0.03). CONCLUSION: The results suggested that the 5-HT2A may play some roles in the effects of drug treatment on OCD.

Adolescent↗

Lack of association between polymorphisms of dopamine receptors, type D2, and bipolar affective illness in a Polish population.

BACKGROUND: Biochemical abnormalities are thought to be important factors causing bipolar disorder. Several lines of evidence suggest dopamine may play a role in its etiology, e.g. depressive syndrome is frequently encountered in subjects affected by Parkinson's disease, where dopamine depletion is observed. Thus the genes of the dopaminergic system are good candidates for studies on bipolar disorder. In the present study, we investigated polymorphisms of dopamine receptors, type D2, including the dopamine receptors D2, D3 and D4. MATERIAL/METHODS: Polish bipolar patients (n=339) and control subjects (n=366) were analyzed for three dopamine receptor gene polymorphisms: dopamine receptor D2 (DRD2) 141 ins/del, dopamine receptor D3 (DRD3) Ser9Gly, and dopamine receptor D4 (DRD4) 521 C/T. RESULTS: Allele and genotype frequencies did not differ significantly among patients and controls. We did not obtain any significant association between the studied polymorphisms and bipolar disorder. CONCLUSIONS: The results suggests that the studied gene variants of type D2 dopamine receptors are not promising candidate genes for bipolar affective illness. We did not consider the family history of the examined subjects, and also the control group was not psychiatrically screened, which may contribute to the lack of significant results.

Adolescent↗

Biochemical markers and genetic research of ADHD.

ADHD (attention hyperactivity disorder) is a polygenetic disorder with various candidate genes. At this time, more than thirty dopaminergic, noradrenergic, serotonergic and GABA-ergic genes are known. The research of only some candidate genes (DRD4, DAT, DRD5, DBH, 5HTT, HTR1B and SNAP25) brought relatively consistent results confirming the heredity of ADHD syndromes. The results of research of other genes (DRD2, DRD3, MAO, ADR2A, GABA A3, GABA B3) are not clear yet. This paper summarizes the most important genetic data in correlations with biochemical periphery parameters (especially for DBH, HVA, MHPG, serotonin). Hypothetically, certain subgroups of ADHD may be identified by correlation of biochemical characteristics and some candidate genes. The paper discusses some implications for future research. Review.

Attention Deficit Disorder with Hyperactivity↗

[Genetic analysis of migraine headache: a review].

Recent advances in genetic analysis of migraine headache are reviewed. Point mutations of P/Q -type Ca2+ channel alpha1 subunit(CACNA1A) gene and Na-K ATPase, alpha2 (ATP1A2) gene have been identified in the familial hemiplegic migraine (FHM-1 and FHM-2, respectively). Mutations in notch-3 gene cause the cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), which is an autosomal dominant inherited disorder often accompanying with migraine like headache. Serotonin (5-HT) related genes, dopamine D2 receptors (DRD2) gene, methylenetetrahydrofolate reductase (MTHFR) gene, and angiotensin converting enzyme (ACE) gene have been noticed as the susceptible genes for migraine pathogenesis. Genetic study of migraine is promising and will provide further understanding of the migraine pathophysiology. Discovery of the responsible or susceptible genes will open an avenue to develop new therapeutic strategy.

CADASIL↗

[Genetic background of ADHD: population studies, genes of the catecholamine system].

Attention-deficit hyperactivity disorder (ADHD) begins in early childhood. In this article we review the studies supporting a genetic background of this disorder. ADHD occurs in 3-10% of the general population. Family studies reveal a 5 times more likely frequency of ADHD among first-degree relatives than in the general population. Monozygotic twin concordance rate for ADHD is 81%, whereas for dizygotic twins it is 29%. One of the ADHD predisposing factors is dopaminergic neurotransmission abnormality. According to other studies there is a relationship between polymorphism of dopamine transporter gene (DAT), dopamine receptors genes: DRD2, DRD3, DRD4, DRD5, dopamine-beta-hydroxylase gene (DBH) and catechol-O-methyltransferase gene (COMT) and ADHD. In other articles authors describe abnormalities of the serotonergic system, such as the polymorphism of the serotonin transporter gene (5HTT/SERT), serotonin receptors genes 5HT2A and 5HT1B in the development ofADHD. Another possible factor in ADHD background is the dysregulation of the adrenergic system. The most frequently studied is the connection between polymorphism of norepinephrine transporter gene (NET), adrenergic receptors genes: alpha 2A (ADRA2A), alpha 1C (ADRA1C), alpha 2C and monoamine oxidase A gene (MAO-A).

Attention Deficit Disorder with Hyperactivity↗

Cell wall lipopolysaccharide response to the ColIb plasmid mutants.

Mutants of ColIb plasmid affected the synthesis of O-side chains of lipopolysaccharides (LPS) in Salmonella. The plasmid srd 25 (defective in colicin synthesis) caused a significant decline of rhamnose and mannose content and lack of abequose in LPS of S. typhimurium. The number of repeating units in O-side chains was decreased after the indroduction of srd 25. Cultures of S. typhimurium and S. enteritidis harboring drd2 (derepressed in colicin production) polymerised dideoxyhexose-defective O-side chains i.e. deprived of abequose and tyvelose, respectively. In dideoxyhexoseless S. meleagridis the content of rhamnose and mannose were reduced. The information for the alterations of Salmonella LPS was contained in the plasmid genome. In the wild-type plasmids the genes controlling the O-antigen changes were not expressed.

Cell Wall↗

Bipolar affective disorder partially cosegregates with a balanced t(9;11)(p24;q23.1) chromosomal translocation in a small pedigree.

Analysis of an extended pedigree in which a balanced t(9;11)(p24;q23.1) translocation was found to cosegregate with bipolar affective disorder revealed that five of 11 translocation carriers had bipolar affective disorder and one carrier had unipolar depression. There were no affected individuals in the pedigree without the balanced translocation. We hypothesized that gene(s) or gene regulatory regions disrupted by the translocation might be contributing to the bipolar affective disorder in a dominant fashion. To test this hypothesis, we isolated the derivative chromosome 9 and derivative chromosome 11 in somatic cell hybrids and identified the nearest flanking markers on chromosome 9 (D9S230 and D9S2011E/HRFX3) and chromosome 11 (EST00652 and CRYA2). YAC contigs were constructed in the region of flanking markers for both chromosomes 9 and 11. Chromosome 11 breakpoint was localized within an 8-kb region in a small insert (100 kb) YAC. Chromosome 9 breakpoint was localized within approximately 2 Mb region. Several genes and ESTs including EST00652, CRYA2, DRD2, 5HTR3 on chromosome 11 and VLDLR and SLC1A1 on chromosome 9 were mapped within the vicinity of the breakpoint but were shown not to be disrupted by the translocation breakpoint. Although several possibilities exist regarding the role of the balanced translocation in developing bipolar affective disorder in this pedigree, including a chance cosegregation, identification of a disrupted gene or gene regulatory region with the help of physical mapping resources described in this study may help to identify the presence of a susceptibility gene for this disorder.

Bipolar Disorder↗