-
Sexual Medicine Reviews Oct 2020A growing number of genetic association studies have been performed to investigate the association between the genetic susceptibility alleles and the risk of premature...
INTRODUCTION
A growing number of genetic association studies have been performed to investigate the association between the genetic susceptibility alleles and the risk of premature ejaculation (PE); however, the results remain inconclusive.
OBJECTIVES
This systematic review aimed: (i) to determine whether an association exists between gene(s) or allelic variant(s) and PE; (ii) to assess whether the associations are consistent across studies in magnitude and direction, and (iii) to identify any limitation, gap, or shortcoming in the included studies.
METHODS
The literature search was conducted in PubMed, MEDLINE, Scopus, Cochrane Library, EMBASE, Academic Search Complete, Google Scholar, and CINAHL databases.
RESULTS
Different gene variants associated with PE were assessed. 25 genetic association studies met the inclusion criteria that investigated 11 genes, 2,624 men with PE compared with 9,346 men as controls, twins, and siblings. 19 studies demonstrated a significant association with PE, whereas 4 studies denied such a relationship. SLC6A4 gene polymorphism was investigated in 11 studies (7 studies demonstrated a significant relationship with PE, and 4 studies denied such a relationship). Dopamine transporter gene (DAT1) polymorphism was investigated in 4 studies exhibiting a significant relationship. Androgen receptor gene polymorphisms were investigated in 2 studies, 1 with a significant relationship and the other with a non-significant relationship. Oxytocin gene polymorphisms and tryptophan hydroxylase 2 gene polymorphisms were investigated in 2 studies with a significant relationship.
CONCLUSION
While this review has highlighted several genes that may be potentially associated with PE such as SLC6A4, limitations such as variance in study methods, lack of robust findings, small sample sizes, lack of reproducibility, quality of reporting, and quality of assessment remain a major concern. Further efforts such as standardizing reporting, exploring complementary designs, and the use of genome-wide association studies technology are warranted to test the reproducibility of these early findings. Mostafa T, Abdel-Hamid IA, Taymour M, et al. Gene Variants in Premature Ejaculation: Systematic Review and Future Directions. Sex Med Rev 2020;8:586-602.
Topics: Dopamine Plasma Membrane Transport Proteins; Genetic Association Studies; Humans; Male; Oxytocin; Polymorphism, Genetic; Premature Ejaculation; Receptors, Androgen; Receptors, Serotonin; Reproducibility of Results; Serotonin Plasma Membrane Transport Proteins; Tryptophan Hydroxylase
PubMed: 32800770
DOI: 10.1016/j.sxmr.2020.07.002 -
Zhurnal Nevrologii I Psikhiatrii Imeni... 2020A systematic review of association studies on the role of single nucleotide variants (SNVs) of the dopaminergic system genes on the effectiveness of clozapine in...
A systematic review of association studies on the role of single nucleotide variants (SNVs) of the dopaminergic system genes on the effectiveness of clozapine in schizophrenia has been perfromed. A search of literature was conducted in PubMed, MedLine, Web of Science Core Collection (Clarivate Analytics), Web of Science, Russian Science Citation Index, Scopus, Scientific Research, Google Scholar, Oxford Press, e-Library from 1995-2019. Association studies of 53 SNPs of genes encoding dopamine receptor isoforms (), dopamine transporter () and catechol-O- methyltransferase (), and the nature of their association with the therapeutic response to clozapine were analyzed. The results of SNPs studies of and genes are the most controversial. This can be explained by the heterogeneity of the samples and the lack of standardization of methods for evaluating the effectiveness of treatment in the context of association studies. The clear population specificity of the association of some SNPs of , and genes with the response to clozapine therapy has been shown. Most of the identified associations are haplotype specific. The obtained regularities of the effect of SNPs of dopaminergic system genes on the effectiveness of clozapine therapy should be considered in an individual approach to treatment of schizophrenia.
Topics: Catechol O-Methyltransferase; Clozapine; Dopamine; Genotype; Humans; Pharmacogenetics; Polymorphism, Single Nucleotide; Russia; Schizophrenia
PubMed: 32790988
DOI: 10.17116/jnevro202012007195 -
Psychiatry Research. Neuroimaging Jun 2020A systematic review was implemented according to PRISMA guidelines on Pubmed, Psychinfo, Medline, Embase to fill the existing literature gap on the effectiveness of...
A systematic review was implemented according to PRISMA guidelines on Pubmed, Psychinfo, Medline, Embase to fill the existing literature gap on the effectiveness of using Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) in Anorexia Nervosa (AN), Bulimia Nervosa (BN) and Binge Eating Disorder (BED). Twenty-two articles were included. Four studies reported an increased density in 5-hydroxytryptamine receptor (5-HT) in fronto-temporo-parietal regions in both affected and recovered AN as well as in BN. The 5-HT transporter (5-HTT) binding was increased or diminished in different specific cortical areas and in relation to Eating Disorder (ED) subtypes. Some evidences of blunted Dopamine (DA) release in the putamen in BN patients suggest that their DA function might be impaired as in addictive behaviours. Studies estimating the regional Cerebral Blood Flow (rCBF) with SPECT demonstrated that temporal areas seem to play a key role in ED corroborating the hypothesis of a cingulate-temporal cortical dysfunction in AN. In addition, alterations of both parietal and prefrontal cortex provide a possible common neural substrate in AN. Studies included in this review are heterogeneous preventing robust conclusions, however, our findings add knowledge on some of the neurotransmitters involved in ED.
Topics: Anorexia Nervosa; Binge-Eating Disorder; Bulimia Nervosa; Cerebrovascular Circulation; Humans; Parietal Lobe; Positron-Emission Tomography; Prefrontal Cortex; Tomography, Emission-Computed, Single-Photon
PubMed: 32234640
DOI: 10.1016/j.pscychresns.2020.111065 -
Biological Psychiatry Oct 2019Many polymorphisms in dopamine genes are reported to affect cognitive, imaging, or clinical phenotypes. It is often inferred or assumed that such associations are... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Many polymorphisms in dopamine genes are reported to affect cognitive, imaging, or clinical phenotypes. It is often inferred or assumed that such associations are causal, mediated by a direct effect of the polymorphism on the gene product itself. However, the supporting evidence is not always clear.
METHODS
We conducted systematic reviews and meta-analyses to assess the empirical evidence for functional polymorphisms in genes encoding dopaminergic enzymes (COMT, DBH, DDC, MAOA, MAOB, and TH), dopamine receptors (DRD1, DRD2, DRD3, DRD4, and DRD5), the dopamine transporter (DAT), and vesicular transporters (VMAT1 and VMAT2). We defined functionality as an effect of the polymorphism on the expression, abundance, activity, or affinity of the gene product.
RESULTS
We screened 22,728 articles and identified 255 eligible studies. We found robust and medium to large effects for polymorphisms in 4 genes. For catechol-O-methyltransferase (COMT), the ValMet polymorphism (rs4680) markedly affected enzyme activity, protein abundance, and protein stability. Dopamine β-hydroxylase (DBH) activity was associated with rs1611115, rs2519152, and the DBH-STR polymorphism. Monoamine oxidase A (MAOA) activity was associated with a 5' VNTR polymorphism. Dopamine D receptor (DRD2) binding was influenced by the Taq1A (rs1800497) polymorphism, and rs1076560 affected DRD2 splicing.
CONCLUSIONS
Some widely studied dopaminergic polymorphisms clearly and substantially affect the abundance or activity of the encoded gene product. However, for other polymorphisms, evidence of such an association is negative, inconclusive, or lacking. These findings are relevant when selecting polymorphisms as "markers" of dopamine function, and for interpreting the biological plausibility of associations between these polymorphisms and aspects of brain function or dysfunction.
Topics: Brain; Dopamine; Dopamine Plasma Membrane Transport Proteins; Humans; Polymorphism, Single Nucleotide; Receptors, Dopamine
PubMed: 31303260
DOI: 10.1016/j.biopsych.2019.05.014 -
Neuroscience and Biobehavioral Reviews Nov 2019A major hypothesis in the addiction field suggests deficits in dopamine signaling during abstinence as a driving mechanism for the relapsing course of the disorder....
A major hypothesis in the addiction field suggests deficits in dopamine signaling during abstinence as a driving mechanism for the relapsing course of the disorder. Paradoxically, blockade of mu-opioid receptors (MORs) intended to suppress dopamine release and alcohol reward is a widely used treatment for preventing relapse in alcohol use disorder (AUD). To elucidate this apparent discrepancy, we systematically survey the literature on experimental studies in AUD subjects and animal models, which assessed striatal dopamine levels and D1, D2-like receptor, dopamine transporter and MOR via positron emission tomography (PET) and ex vivo receptor binding assays. The reported evidence indicates a changing dopaminergic signaling over time, which is associated with concomitant alterations in MOR, thus suggesting a highly dynamic regulation of the reward system during abstinence. Such a view can reconcile the various evidences from in vivo and postmortem studies, but makes developing an effective pharmacological intervention that specifically targets either dopamine receptors or the transporter system a daunting task.
Topics: Alcoholism; Animals; Autopsy; Craving; Humans; Positron-Emission Tomography; Receptors, Dopamine; Receptors, Opioid, mu; Reward
PubMed: 30243576
DOI: 10.1016/j.neubiorev.2018.09.010