scholarly journals Underlying Susceptibility to Eating Disorders and Drug Abuse: Genetic and Pharmacological Aspects of Dopamine D4 Receptors

Nutrients ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2288 ◽  
Author(s):  
Luca Botticelli ◽  
Emanuela Micioni Di Bonaventura ◽  
Fabio Del Bello ◽  
Gianfabio Giorgioni ◽  
Alessandro Piergentili ◽  
...  
Keyword(s):  
Drug Abuse ◽  
Eating Behaviors ◽  
Tandem Repeats ◽  
Drugs Of Abuse ◽  
Brain Area ◽  
Variable Number ◽  
Intracellular Response ◽  
D4 Receptor ◽  
Maladaptive Eating

The dopamine D4 receptor (DRD4) has a predominant expression in the prefrontal cortex (PFC), brain area strictly involved in the modulation of reward processes related to both food and drug consumption. Additionally, the human DRD4 gene is characterized by a variable number of tandem repeats (VNTR) in the exon 3 and, among the polymorphic variants, the 7-repeat (7R) allele appears as a contributing factor in the neurobiological mechanisms underlying drug abuse, aberrant eating behaviors and related comorbidities. The 7R variant encodes for a receptor with a blunted intracellular response to dopamine, and carriers of this polymorphism might be more tempted to enhance dopamine levels in the brain, through the overconsumption of drugs of abuse or palatable food, considering their reinforcing properties. Moreover, the presence of this polymorphism seems to increase the susceptibility of individuals to engage maladaptive eating patterns in response to negative environmental stimuli. This review is focused on the role of DRD4 and DRD4 genetic polymorphism in these neuropsychiatric disorders in both clinical and preclinical studies. However, further research is needed to better clarify the complex DRD4 role, by using validated preclinical models and novel compounds more selective for DRD4.

scholarly journals Association between the dopamine D4 receptor gene exon III variable number of tandem repeats and political attitudes in female Han Chinese

2015 ◽  
Vol 282 (1813) ◽  
pp. 20151360
Author(s):  
Richard P. Ebstein ◽  
Mikhail V. Monakhov ◽  
Yunfeng Lu ◽  
Yushi Jiang ◽  
Poh San Lai ◽  
...  
Keyword(s):  
Individual Differences ◽  
Tandem Repeats ◽  
Political Attitudes ◽  
Receptor Gene ◽  
Variable Number ◽  
Han Chinese ◽  
Political Attitude ◽  
Dopamine D4 Receptor ◽  
The Social ◽  
D4 Receptor

Twin and family studies suggest that political attitudes are partially determined by an individual's genotype. The dopamine D4 receptor gene ( DRD4 ) exon III repeat region that has been extensively studied in connection with human behaviour, is a plausible candidate to contribute to individual differences in political attitudes. A first United States study provisionally identified this gene with political attitude along a liberal–conservative axis albeit contingent upon number of friends. In a large sample of 1771 Han Chinese university students in Singapore, we observed a significant main effect of association between the DRD4 exon III variable number of tandem repeats and political attitude. Subjects with two copies of the 4-repeat allele (4R/4R) were significantly more conservative. Our results provided evidence for a role of the DRD4 gene variants in contributing to individual differences in political attitude particularly in females and more generally suggested that associations between individual genes, and neurochemical pathways, contributing to traits relevant to the social sciences can be provisionally identified.

A Variable-Number-of-Tandem-Repeats Polymorphism in the Dopamine D4 Receptor Gene Affects Social Adaptation of Alcohol Use

2010 ◽  
Vol 21 (8) ◽  
pp. 1064-1068 ◽  
Author(s):  
Helle Larsen ◽  
Carmen S. van der Zwaluw ◽  
Geertjan Overbeek ◽  
Isabela Granic ◽  
Barbara Franke ◽  
...  
Keyword(s):  
Alcohol Use ◽  
Tandem Repeats ◽  
Receptor Gene ◽  
Variable Number ◽  
Social Adaptation ◽  
Dopamine D4 Receptor ◽  
D4 Receptor

scholarly journals Use of Multilocus Variable Number of Tandem Repeats Analysis Genotyping to Determine the Role of Asymptomatic Carriers in Clostridium difficile Transmission

2013 ◽  
Vol 57 (8) ◽  
pp. 1094-1102 ◽  
Author(s):  
Scott R. Curry ◽  
Carlene A. Muto ◽  
Jessica L. Schlackman ◽  
A. William Pasculle ◽  
Kathleen A. Shutt ◽  
...  
Keyword(s):  
Clostridium Difficile ◽  
Tandem Repeats ◽  
Variable Number ◽  
Asymptomatic Carriers

scholarly journals Characterisation of Neisseria meningitidis C strains causing two clusters in the north of Italy in 2007 and 2008

2009 ◽  
Vol 14 (16) ◽  
Author(s):  
C Fazio ◽  
A Neri ◽  
T Sofia ◽  
A Carannante ◽  
M G Caporali ◽  
...  
Keyword(s):  
Tandem Repeats ◽  
Clonal Complex ◽  
Fatal Outcome ◽  
Variable Number ◽  
The North ◽  
Surveillance Report ◽  
Laboratory Surveillance ◽  
Sporadic Cases ◽  
Variable Number Tandem Repeats

Two clusters of invasive meningococcal disease in the north of Italy both due to serogroup C/ST-11 clonal complex are here described. The objective of the investigation was to analyse the phenotype and the genotype of meningococci involved in the two clusters which were of national relevance due to the fatal outcome of the majority of cases (six of the total of 10 cases). All the strains were C:2a:P1.5 ST-11/ET-37 clonal complex. Two pulsed field gel electrophoresis (PFGE) and variable number tandem repeats (VNTR) profiles were identified, one for each cluster. VNTRs were different from those detected in Italy for C/ST-11 strains isolated from sporadic cases in the same period. This laboratory surveillance report highlights the importance and the crucial role of molecular characterisation to confirm the relatedness among meningococci responsible for clusters of cases.

scholarly journals Dysglycemia is associated with Mycobacterium tuberculosis lineages in tuberculosis patients of North Lima - Peru

2020 ◽  
Author(s):  
Kattya Lopez ◽  
María B. Arriaga ◽  
Juan G. Aliaga ◽  
Nadia N. Barreda ◽  
Oswaldo M. Sanabria ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Pulmonary Tuberculosis ◽  
Latin American ◽  
Tandem Repeats ◽  
Scientific Evidence ◽  
Variable Number ◽  
Health Care Facilities ◽  
Variable Number Tandem Repeats ◽  
Epidemiological Characteristics

AbstractThis study was performed to investigate the role of dysglycemia on the genetic diversity of Mycobacterium tuberculosis (MTB) among pulmonary tuberculosis (TB) patients to build scientific evidence about the possible mechanisms of TB transmission. MTB isolates obtained of patients affected by pulmonary tuberculosis from health care facilities of North Lima - Peru, were analyzed using whole genome sequencing and 24-locus mycobacterial interspersed repetitive-unit-variable-number tandem repeats (MIRU-VNTR). Subsequently, clinical and epidemiological characteristics were associated with clustering, lineages and comorbid conditions. The analysis carried out 112 pulmonary TB patients from various health centers in North Lima, 17 (15%) had diabetes mellitus (DM) and 33 (29%) had pre-diabetes (PDM). Latin American-Mediterranean, Haarlem and Beijing were the most frequent MTB lineages found in those patients. Previous TB (adjusted odds ratio [aOR]=3.65; 95%CI: 1.32-17.81), age (aOR=1.12; 95%CI: 1.03-1.45) and Beijing lineage (aOR=3.53; 95%CI: 1.08-13.2) were associated with TB-DM comorbidity. Alcoholism (aOR=2.92; 95%CI: 1.10-8.28), age (aOR=1.05; 95%CI: 1.03-1.12) and Haarlem lineage (aOR=2.54; 95%CI: 1.04-6.51) were associated with TB-PDM comorbidity. Beijing and Haarlem lineages were independently associated with TB-DM and TB-PDM comorbidities, respectively. Although these findings may be surprising, we must be cautious to suggest that dysglycemia could be associated with a highly clustering and predisposition of MTB lineages related to a serious impact on the severity of TB disease, which requires further research.

scholarly journals Drugs of abuse and blood-brain barrier endothelial dysfunction: A focus on the role of oxidative stress

2015 ◽  
Vol 36 (3) ◽  
pp. 539-554 ◽  
Author(s):  
Ravi K Sajja ◽  
Shafiqur Rahman ◽  
Luca Cucullo
Keyword(s):  
Oxidative Stress ◽  
Drug Abuse ◽  
Blood Brain Barrier ◽  
Drugs Of Abuse ◽  
Brain Barrier ◽  
Molecular Pathways ◽  
Blood Brain ◽  
Increased Risk

Psychostimulants and nicotine are the most widely abused drugs with a detrimental impact on public health globally. While the long-term neurobehavioral deficits and synaptic perturbations are well documented with chronic use of methamphetamine, cocaine, and nicotine, emerging human and experimental studies also suggest an increasing incidence of neurovascular complications associated with drug abuse. Short- or long-term administration of psychostimulants or nicotine is known to disrupt blood-brain barrier (BBB) integrity/function, thus leading to an increased risk of brain edema and neuroinflammation. Various pathophysiological mechanisms have been proposed to underlie drug abuse-induced BBB dysfunction suggesting a central and unifying role for oxidative stress in BBB endothelium and perivascular cells. This review discusses drug-specific effects of methamphetamine, cocaine, and tobacco smoking on brain microvascular crisis and provides critical assessment of oxidative stress-dependent molecular pathways focal to the global compromise of BBB. Additionally, given the increased risk of human immunodeficiency virus (HIV) encephalitis in drug abusers, we have summarized the synergistic pathological impact of psychostimulants and HIV infection on BBB integrity with an emphasis on unifying role of endothelial oxidative stress. This mechanistic framework would guide further investigations on specific molecular pathways to accelerate therapeutic approaches for the prevention of neurovascular deficits by drugs of abuse.

scholarly journals Associations Between the Dopamine D4 Receptor and DAT1 Dopamine Transporter Genes Polymorphisms and Personality Traits in Addicted Patients

2018 ◽  
Vol 15 (10) ◽  
pp. 2076 ◽  
Author(s):  
Jolanta Chmielowiec ◽  
Krzysztof Chmielowiec ◽  
Aleksandra Suchanecka ◽  
Grzegorz Trybek ◽  
Bożena Mroczek ◽  
...  
Keyword(s):  
Personality Traits ◽  
Tandem Repeats ◽  
Statistical Significance ◽  
Variable Number ◽  
Case Group ◽  
Dopamine System ◽  
Mesolimbic Dopamine System ◽  
Dopaminergic Transmission ◽  
D4 Receptor ◽  
Main Effects

Many factors are involved in addiction. The dopaminergic system is thought to be the key element in this process. The mesolimbic dopamine system is a crucial element in the reward system. Changes in this system are thought to be leading to substance use disorders and dependence. Therefore, for our study we chose an analysis of two polymorphisms in genes (Variable Number of Tandem Repeats in DRD4 and DAT1) responsible for dopaminergic transmission, which might be implicated in the scores of personality traits measured by the NEO-FFI test. The study group consisted of 600 male volunteers—299 addicted subjects and 301 controls. Both groups were recruited by psychiatrists; in the case group addiction was diagnosed; in the controls a mental illness was excluded. In both groups the same psychometric test and genotyping by the PCR VNTR method were performed. The results were investigated by a multivariate analysis of the main effects ANOVA. In the presented study no DRD4 main effects were found for any of the analyzed traits but the DRD4 main effects approximated to the statistical significance for the extraversion scale. However, no DAT1 main effects were found for any of the analyzed traits but the DAT1 main effects approximated to the statistical significance for the agreeability scale.These associations open new possibilities for addiction research.

Novel variable number of tandem repeats of gibbon MAOA gene and its evolutionary significance

Genome ◽  
2014 ◽  
Vol 57 (8) ◽  
pp. 427-432 ◽  
Author(s):  
Yuri Choi ◽  
Yi-Deun Jung ◽  
Selvam Ayarpadikannan ◽  
Akihiko Koga ◽  
Hiroo Imai ◽  
...  
Keyword(s):  
Evolutionary History ◽  
Tandem Repeats ◽  
Luciferase Activity ◽  
Variable Number ◽  
Monoamine Oxidase A ◽  
Evolutionary Significance ◽  
Maoa Gene ◽  
Nomascus Concolor ◽  
Luciferase Activity Assay

Variable number of tandem repeats (VNTRs) are scattered throughout the primate genome, and genetic variation of these VNTRs have been accumulated during primate radiation. Here, we analyzed VNTRs upstream of the monoamine oxidase A (MAOA) gene in 11 different gibbon species. An abundance of truncated VNTR sequences and copy number differences were observed compared to those of human VNTR sequences. To better understand the biological role of these VNTRs, a luciferase activity assay was conducted and results indicated that selected VNTR sequences of the MAOA gene from human and three different gibbon species (Hylobates klossii, Hylobates lar, and Nomascus concolor) showed silencing ability. Together, these data could be useful for understanding the evolutionary history and functional significance of MAOA VNTR sequences in gibbon species.

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