Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.3.1.107 (DAT)
 1,471 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Attention-deficit Hyperactivity disorder (ADHD) is a multifactorial disorder clinically characterized by inattentiveness, impulsivity and hyperactivity. The occurrence of this disorder is between 3 and 6% of the children population, with boys predominating over girls at a ratio of 3:1 or more. The research of some candidate genes (DRD4, DAT, DRD5, DBH, 5HTT, HTR1B and SNAP25) brought consistent results confirming the heredity of ADHD syndromes. Dopamine-beta-hydroxylase (DBH) is an enzyme responsible for the conversion of dopamine into noradrenaline. Alteration of the dopamine/noradrenaline levels can result in hyperactivity. The DBH protein is released in response to stimulation. DBH activity, derived largely from sympathetic nerves, can be measured in human plasma. Patients with ADHD showed decreased activities of DBH in serum and urine. Low DBH levels correlate indirectly with the seriousness of the hyperkinetic syndrome in children [19,20]. In the DBH gene, the G444A, G910T, C1603T, C1912T, C-1021T, 5 -ins/del and TaqI polymorphisms occur frequently and may affect the function of gene products or modify gene expression and thus influence the progression of ADHD. This article reviews the DBH itself and polymorphisms in the DBH gene that influence the DBH activity in the serum and the CSF level of DBH. All those are evaluated in connection with ADHD.
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PMID:Polymorphisms and low plasma activity of dopamine-beta-hydroxylase in ADHD children. 1718 1

It is widely accepted that dopamine and serotonin (5-HT) neurotransmission can be critically involved in the development of alcohol abuse and alcohol dependence. Lesch's typology of alcoholism has been gaining increasing popularity as it qualitatively differentiates patients into different treatment response subgroups. The aim of the present study was to evaluate a possible genetic background of Lesch's typology with special emphasis placed on dopamine- and serotonin-related genes. 122 alcoholics (the mean age: 35+/-9 years) were investigated. According to Lesch's typology, 58 patients were of type I, 36 patients of type II, 11 patients of type III, and 17 patients of type IV. Alcohol drinking and family history was assessed by means of a structured interview, based on the Semi-Structured Assessment for the Genetics of Alcoholism. 150 control subjects without psychiatric disorders were also recruited. The control group was ethnically-, age- and gender-matched to the patients. The DRD2 TaqIA, exon 8, and promoter -141C ins/del polymorphisms as well as COMT Val158Met, 5HTT 44 bp del in promoter, and DAT 40 bp VNTR polymorphisms were detected by means of PCR. No significant differences were observed when the whole group of alcoholics and the controls were compared. Similarly, there were no differences between either the Lesch type I or type II alcoholics and the control subjects. No significant differences were observed between type I and type II alcoholics. Alleles frequencies were not calculated for the Lesch type III and type IV alcoholics since the number of patients was too small. The present results argue against any major role of the investigated polymorphisms in either Lesch type I or type II alcoholism. More comprehensive studies are needed to define the role of the investigated polymorphisms in Lesch type III and type IV alcoholism.
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PMID:Genetics of Lesch's typology of alcoholism. 1792 19

Background: Approximately 25-50% of people diagnosed with substance use disorder experience psychiatric disorders, and this percentage is even higher if subclinical psychopathological symptomatology is taken into consideration. "Dual diagnosis" implies the comorbidity of two disorders (mental disorder and addiction), but in a clinical setting, numerous dual diagnoses involve multiple addictions (polysubstance use means the concurrent use of more than one psychoactive substance). Clinical observations and epidemiological studies showed that the use of stimulants in combination with other substances results in additional risks. Apart from the clinical significance of the specificity of stimulants used in combination with other substances, only non-exhaustive research on the specificity of this comorbidity has been performed to date. The aim of the study was to analyze polymorphisms of the genes (DRD4 VNTR in exon III Ex3, DRD2 rs1076560, rs1800498, rs1079597, rs6276, as well as in the PROM promoter region (rs1799732, ANKK1 Tag1A rs1800497, DAT) in a group of patients diagnosed with polysubstance use disorder, including addiction to stimulants, and the co-occurrence of specific mental disorders in a group of patients diagnosed with polysubstance use disorder, including addiction to stimulants, compared to the group of patients diagnosed with polysubstance use disorder. Methods: The study group consisted of 601 male volunteers with psychoactive substance dependence (n = 300) and non-dependent controls (n = 301). The genomic DNA was extracted from venous blood using standard procedures. Genotyping was conducted with the real-time PCR method. All computations were performed using STATISTICA 13. Results: Psychotic disorders were significantly more common in the group of males with polysubstance addiction, including addiction to stimulants, compared to the group of males with polysubstance addiction without addiction to stimulants. In our own research, different statistical significances were found in the frequency of the DRD4 Ex3 gene polymorphism: s/s was more common in the study group. Psychotic disorders were more common in people addicted to stimulants compared to people addicted to other substances. Conclusions: In our study, psychotic disorders occurred more frequently in the study group of patients with polysubstance addiction, including addiction to stimulants, compared to the control group of patients with polysubstance addiction, but with no addiction to stimulants. Different statistical significances were found in the frequency of the DRD4 Ex3 gene polymorphism: s/s was more common in the study group, while the l/l genotype was less frequent in the study group. In DRD2 PROM rs 1799732, the del allele occurred more often than the ins allele in the study group. In the DRD4 Ex3 gene polymorphism, the s allele was more common in the study group, and the l allele was less frequent. In the DRD4 Ex3 gene polymorphism for the s/s genotype, psychotic disorders and generalized anxiety were more common, while for the s/l and l/l genotype, they were less frequent. The DRD4 Ex3 polymorphism s alleles were more common for depressive episode, dysthymia, and psychotic disorders as well as generalized anxiety disorder. We see a clear genetic aspect here. However, we want to be careful and draw no definite conclusions.
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PMID:DRD4, DRD2, DAT1, and ANKK1 Genes Polymorphisms in Patients with Dual Diagnosis of Polysubstance Addictions. 3317 85