Association of DRD4 exon III and 5-HTTLPR VNTR genetic polymorphisms with psychiatric symptoms in hemodialysis patients

Alshogran, Osama Y.; AL-Eitan, Laith N.; Altawalbeh, Shoroq M.; Aman, Hatem A

doi:10.1371/journal.pone.0249284

Cited by 3 publications

(2 citation statements)

References 42 publications

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“…Several studies have provided contradicting reports on the impact of lithium on function of the muscarinic receptor. It has been reported [ 77 ] that lithium obstructs the super sensitivity of the muscarinic receptor despite influencing the quantity of receptor within restricted areas, suggesting that it works at a postreceptor site [ 78 , 79 ].…”

Section: Gpcrs and Mood Disordersmentioning

confidence: 99%

Insights into the Promising Prospect of G Protein and GPCR-Mediated Signaling in Neuropathophysiology and Its Therapeutic Regulation

Rahman

Islam

Mim

et al. 2022

Oxidative Medicine and Cellular Longevity

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G protein-coupled receptors (GPCRs) are intricately involved in the conversion of extracellular feedback to intracellular responses. These specialized receptors possess a crucial role in neurological and psychiatric disorders. Most nonsensory GPCRs are active in almost 90% of complex brain functions. At the time of receptor phosphorylation, a GPCR pathway is essentially activated through a G protein signaling mechanism via a G protein-coupled receptor kinase (GRK). Dopamine, an important neurotransmitter, is primarily involved in the pathophysiology of several CNS disorders; for instance, bipolar disorder, schizophrenia, Parkinson’s disease, and ADHD. Since dopamine, acetylcholine, and glutamate are potent neuropharmacological targets, dopamine itself has potential therapeutic effects in several CNS disorders. GPCRs essentially regulate brain functions by modulating downstream signaling pathways. GPR6, GPR52, and GPR8 are termed orphan GPCRs because they colocalize with dopamine D1 and D2 receptors in neurons of the basal ganglia, either alone or with both receptors. Among the orphan GPCRs, the GPR52 is recognized for being an effective psychiatric receptor. Various antipsychotics like aripiprazole and quetiapine mainly target GPCRs to exert their actions. One of the most important parts of signal transduction is the regulation of G protein signaling (RGS). These substances inhibit the activation of the G protein that initiates GPCR signaling. Developing a combination of RGS inhibitors with GPCR agonists may prove to have promising therapeutic potential. Indeed, several recent studies have suggested that GPCRs represent potentially valuable therapeutic targets for various psychiatric disorders. Molecular biology and genetically modified animal model studies recommend that these enriched GPCRs may also act as potential therapeutic psychoreceptors. Neurotransmitter and neuropeptide GPCR malfunction in the frontal cortex and limbic-related regions, including the hippocampus, hypothalamus, and brainstem, is likely responsible for the complex clinical picture that includes cognitive, perceptual, emotional, and motor symptoms. G protein and GPCR-mediated signaling play a critical role in developing new treatment options for mental health issues, and this study is aimed at offering a thorough picture of that involvement. For patients who are resistant to current therapies, the development of new drugs that target GPCR signaling cascades remains an interesting possibility. These discoveries might serve as a fresh foundation for the creation of creative methods for pharmacologically useful modulation of GPCR function.

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Section: Gpcrs and Mood Disordersmentioning

confidence: 99%

Insights into the Promising Prospect of G Protein and GPCR-Mediated Signaling in Neuropathophysiology and Its Therapeutic Regulation

Rahman

Islam

Mim

et al. 2022

Oxidative Medicine and Cellular Longevity

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show abstract

“…We selected functional genetic variants with proven or predicted effects on transcription, translation or protein function with the minor allele frequency (MAF) above 10%. Data on the variants' function were obtained from the available literature [29,30] or with the use of the SNP function prediction tool [31]. Genetic variants were also selected based on their previously reported associations with PD susceptibility, the investigated phenotypes, and with phenotypes similar to those.…”

Section: Single Nucleotide Polymorphism (Snp) Selectionmentioning

confidence: 99%

Serotonin-Related Functional Genetic Variants Affect the Occurrence of Psychiatric and Motor Adverse Events of Dopaminergic Treatment in Parkinson’s Disease: A Retrospective Cohort Study

Redenšek

Blagus

Trošt

et al. 2022

JPM

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The serotonergic system is important in Parkinson’s disease (PD) pathogenesis as it can take over dopamine production after a large portion of dopaminergic neurons is lost through neurodegeneration. The aim of this study was to evaluate the effect of genetic variability of serotonergic genes on the occurrence of motor complications and psychiatric adverse events (AE) due to dopaminergic treatment. We enrolled 231 patients and their clinical data were collected. Genotyping was performed for eight genetic variants. Logistic regression was used for analysis. Carriers of the HTR1A rs6295 GC genotype (OR = 2.58; 95% CI = 1.15–5.78; p = 0.021), TPH2 rs4290270 AA genotype (OR = 2.78; 95% CI = 1.08–7.03; p = 0.034), and at least one TPH2 rs4570625 T allele (OR = 1.86; 95% CI = 1.00–3.44; p = 0.047) had increased risk for visual hallucinations (VH). Additionally, carriers of at least one SLC6A4 5-HTTPLR rs25531 S (OR = 0.52; 95% CI = 0.28–0.96; p = 0.037) or at least one LG allele (OR = 0.37; 95% CI = 0.14–0.97; p = 0.044) had a decreased chance for VH. Constructed haplotypes of the TPH2 showed increased risk for VH (OR = 1.94; 95% CI = 1.06–3.55; p = 0.032) and impulse control disorders (OR = 5.20; 95% CI = 1.86–14.50; p = 0.002). Finally, individual gene–gene interactions showed decreased odds for the development of motor AE. Our findings suggest that the serotonergic pathway may play an important role in the development of AE resulting from dopaminergic treatment.

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DNA Sequence Variations Affecting Serotonin Transporter Transcriptional Regulation and Activity: Do They Impact Alcohol Addiction?

Ferraguti,

Francati,

Codazzo

et al. 2024

IJMS

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Genetic features of alcohol dependence have been extensively investigated in recent years. A large body of studies has underlined the important role of genetic variants not only in metabolic pathways but also in the neurobiology of alcohol dependence, mediated by the neuronal circuits regulating reward and craving. Serotonin transporter (5-HTT), encoded by the SLC6A4 gene (Solute carrier family 6-neurotransmitter transporter-member 4), is targeted by antidepressant drugs such as selective serotonin reuptake inhibitors (SSRIs) and plays a pivotal role in serotoninergic transmission; it has been associated with psychiatric diseases and alcohol dependence. Transcriptional regulation and expression of 5-HTT depend not only on epigenetic modifications, among which DNA methylation (CpG and non-CpG) is primarily involved, but also on sequence variations occurring in intron/exon regions and in untranslated regions in 5′ and 3′, being the first sequences important for the splicing machinery and the last for the binding of transcription factors and micro RNAs. This work intends to shed light on the role of sequence variations known to affect the expression or function of 5-HTT in alcohol-dependent individuals. We found a statistically significant difference in the allelic (p = 0.0083) and genotypic (p = 0.0151) frequencies of the tri-allelic polymorphism, with higher function alleles and genotypes more represented in the control population. Furthermore, we identified three haplotypes more frequent in subjects with AUD (p < 0.0001) and one more frequent in the control population (p < 0.0001). The results obtained for the tri-allelic polymorphism in alcohol dependence confirm what is already present in part of the literature. The role of haplotypes requires further studies to be clarified.

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Association of DRD4 exon III and 5-HTTLPR VNTR genetic polymorphisms with psychiatric symptoms in hemodialysis patients

Cited by 3 publications

References 42 publications

Insights into the Promising Prospect of G Protein and GPCR-Mediated Signaling in Neuropathophysiology and Its Therapeutic Regulation

Insights into the Promising Prospect of G Protein and GPCR-Mediated Signaling in Neuropathophysiology and Its Therapeutic Regulation

Serotonin-Related Functional Genetic Variants Affect the Occurrence of Psychiatric and Motor Adverse Events of Dopaminergic Treatment in Parkinson’s Disease: A Retrospective Cohort Study

DNA Sequence Variations Affecting Serotonin Transporter Transcriptional Regulation and Activity: Do They Impact Alcohol Addiction?

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