catechol-O-methyltransferase Research Articles

Inhibition of catechol-O-methyltransferase (COMT) by heparin oligosaccharides with specific structures

COMT inhibitors are commonly used to improve the effectiveness of levodopa in treating Parkinson's disease by inhibiting its conversion to 3-O-methyldopa. Because of the serious side effect of nitrocatechol COMT inhibitors, it is necessary to develop non-nitrocatechol COMT inhibitors with a higher safety profile. Heparin has been observed to bind to COMT. However, the exact functional significance of this interaction is not fully understood. In this study, the contribution of different substitution of heparin to its binding with COMT was investigated. In vitro and in vivo, heparin oligosaccharides can bind to COMT and inhibit its activity. Furthermore, we enriched the functional heparin oligosaccharides that bind to COMT and identified the sequence UA2S-GlcN(S/Ac)6(S/H)-UA2S-GlcNS6(S/H)-UA2(S/H)-GlcNS6S as the characteristic structural domain of these functional oligosaccharides. This study has elucidated the relationship between the structure of heparin oligosaccharides and their activity against COMT, providing valuable insights for the development of non-nitrocatechol COMT inhibitors with improved safety and efficacy.

Unraveling the Role of COMT Polymorphism in Dopamine-Mediated Vasopressor Effects: An Observational Cross-Sectional Study.

To evaluate the association between rs4680 polymorphism in the COMT gene and the vasoconstrictive effects of commonly used vasopressors. Dopamine is a medication that is given intravenously to critically ill patients to help increase blood pressure. Catechol O-Methyl Transferase (COMT) breaks down dopamine and other catecholamines. There is a genetic variation in the COMT gene called rs4680 that can affect how well the enzyme works. Studies have shown that people with this genetic variation may have different blood pressure levels. However, no one has looked at how this genetic variation affects the way dopamine works to increase blood pressure. To investigate the impact of the rs4680 polymorphism in the COMT gene on the pharmacodynamic response to dopamine. Critically ill patients administered dopamine were included following the consent of their legally acceptable representatives. Details on their demographic characteristics, diagnosis, drug-related details, changes in the heart rate, blood pressure, and urinary output were obtained. The presence of rs4680 polymorphism in the COMT gene was evaluated using a validated method. One hundred and seventeen patients were recruited, and we observed a prevalence of rs4680 polymorphism in 57.3% of our critically ill patients. Those with mutant genotypes were observed with an increase in the median rate of change in mean arterial pressure (mm Hg/hour) [wild: 8.9 (-22.6 to 49.1); heterozygous mutant: 5.9 (-34.1 to 61.6); and homozygous mutant: 19.5 (-2.5 to 129.2)] and lowered urine output (ml/day) [wild: 1080 (21.4 to 5900); heterozygous mutant: 380 (23.7 to 15800); and homozygous mutant: 316.7 (5.8 to 2308.3)]. V158M (rs4680) polymorphism is widely prevalent in the population and was significantly associated with altered effects as observed clinically. This finding suggests valuable insights into the molecular basis of COMT function and its potential impact on neurotransmitter metabolism and related disorders. Large-scale studies delineating the effect of these polymorphisms on various vasopressors are the need of the hour.

#108 - - Bioethical Considerations for COMT gene Polymorphisms Testing in Psychotropic Drug Users

#108 - - Bioethical Considerations for COMT gene Polymorphisms Testing in Psychotropic Drug Users

Search for Association of Polymorphisms rs6280 of the DRD3 Gene, rs4680 of the COMT Gene, rs6265 of the Gene BDNF with Schizophrenia Resistant to Antipsychotic Therapy in Russian Populations

Background: resistant schizophrenia, despite the introduction of new antipsychotics and diagnostic methods, still reaches 50%of cases among all patients with schizophrenia. The search for new methods of early diagnosis using personalized genetic analysis tools seems relevant and promising at the present time. The aim of the study was to analyze the associations of polymorphisms COMT rs4680, DRD3 rs6280, BDNF rs6265 with the development of a therapeutic resistance in patients with schizophrenia. Patients and methods: а real-time genetic analysis of 264 patients with schizophrenia examined by clinical and psychometric methods. A prospective follow-up for 6 weeks was carried out with further division of the sample into 2 groups: respondents and patients with resistance based on the evaluation of the effectiveness of psychopharmacotherapy. Results: a significant association with the ineffectiveness of psychopharmacotherapy found in patients with schizophrenia being homozygotes in the recessive model and being heterozygotes in the codominant model of the rs6265 polymorphism of the BDNF gene. Conclusions: the rs6265 polymorphism of the BDNF gene can be considered as a diagnostic marker for the development of treatment resistant schizophrenia, but requires further study to confirm sensitivity and specificity.

Nitrophenols disrupt the expression and activity of biotransformation enzymes (CYP3A and COMT) in chicken ovarian follicles in vivo and in vitro.

Nitrophenols are environmental pollutants and xenobiotics, the main sources of which are diesel exhaust fumes and pesticides. The biotransformation processes that take place in the liver are defence mechanisms against xenobiotics, such as nitrophenols. Our previous study showed that the chicken ovary is an additional xenobiotic detoxification place and that nitrophenols disrupt steroidogenesis in chicken ovarian follicles. Therefore, the present study aimed to determine the in vivo and in vitro effects of 4-nitrophenol (PNP) and 3-methyl-4-nitrophenol (PNMC) on the expression and activity of phase I (CYP3A) and phase II (COMT) biotransformation enzymes in chicken ovary. In an in vivo study, hens were treated with a vehicle or 10mg PNP or PNMC/kg b.wt. per day for 6 days. In an in vitro study, prehierarchical white and yellowish follicles, as well as the granulosa and theca layers of the three largest preovulatory follicles (F3, F2 and F1), were isolated and then incubated in a control medium or medium supplemented with PNP (10-6M) or PNMC (10-6M) for 24 or 48 h. Both in vivo and in vitro studies showed that nitrophenols exert tissue- and compound-dependent (PNP or PNMC) effects on CYP3A and COMT gene (real-time PCR) protein (Western blot) expression and their activity (colorimetric methods). The inhibitory effect of nitrophenols in vivo on the activity of biotransformation enzymes suggest that the ovary has the capacity to metabolise PNP and PNMC.

To Each His Own Fear: Gender-Related Association of Anxiety, Substance Use, and Eating Disorders in a Representative Birth Cohort Sample of Young Adults with Either COMT Val158Met allele

Introduction: The role of catechol-O-methyltransferase (COMT) in catecholamine neurotransmitter metabolism has led to the investigation of variants of the corresponding gene in the etiology of different psychiatric disorders, but the results are inconclusive. Methods: We have examined the relationship between COMT Val158Met single nucleotide polymorphism (rs4680) and the occurrence of psychiatric disorders in a highly representative birth cohort sample of young adults in the Estonian Children Personality Behaviour and Health Study (original n = 1,238). The lifetime occurrence of psychiatric disorders at the age of 25 years was assessed with the Mini-International Neuropsychiatric Interview. Results: Both Val- and Met-alleles of the COMT Val158Met were associated with specific psychiatric disorders. Met-allele carriers had a significantly higher occurrence of agoraphobia (3.2% vs. 0.5%; χ² = 4.10; p < 0.05) compared to Val/Val homozygotes. Also, the occurrence of panic disorder was significantly higher in female Met-allele carriers than in Val/Val homozygote females (10.2% vs. 3.6%; χ² = 4.62 p = 0.03). In contrast, the occurrence of generalized anxiety disorder was higher in Val/Val females when compared to Met-allele carriers (12.7% vs. 6.8%; χ² = 4.16; p = 0.04). Also, female Val/Val homozygotes (15.5%) had a higher occurrence of eating disorders than Met-allele carriers (6.1%) of the COMT Val158Met polymorphism (χ² = 10.39; p = 0.002). In the whole sample, Met-allele homozygotes had a higher occurrence of alcohol use and substance use disorders than Val-allele carriers (χ² = 3.62 and 3.68, respectively; p < 0.05). Conclusion: In a regional highly birth cohort representative sample, either COMT rs4680 variant was observed in association with specific psychiatric disorders.

HR/MS-based lipidome analysis of rat brain modulated by tolcapone

Lipids play key roles in the body, influencing cellular regulation, function, and signalling. Tolcapone, a potent catechol-O-methyltransferase (COMT) inhibitor described to enhance cognitive performance in healthy subjects, was previously shown to impact fatty acid β-oxidation and oxidative phosphorylation. However, its impact on the brain lipidome remains unexplored. Hence, this study aimed to assess how tolcapone affects the lipidome of the rat pre-frontal cortex (PFC), a region of the brain highly relevant to tolcapone therapeutic effect, while evaluating its influence on operant behaviour. Tolcapone at 20 mg/kg was chronically administered to Wistar rats during a behavioural task and an untargeted liquid chromatography high-resolution mass spectrometry (LC-HR/MS) approach was employed to profile lipid species. The untargeted analysis identified 7227 features, of which only 33% underwent statistical analysis following data pre-processing. The results revealed an improved cognitive performance and a lipidome remodelling promoted by tolcapone. The lipidomic analysis showed 32 differentially expressed lipid species in tolcapone-treated animals (FC ≥ 1.2, p-value ≤ 0.1), and among these several triacylglycerols, cardiolipins and N-acylethanolamine (NAE 16:2) were found upregulated whereas fatty acids, hexosylceramides, and several phospholipids including phosphatidylcholines and phosphatidylethanolamines were downregulated. These preliminary findings shed light on tolcapone impact on lipid pathways within the brain. Although tolcapone improved cognitive performance and literature suggests the significance of lipids in cognition, this study did not conclusively establish that lipids directly drove or contributed to this outcome. Nevertheless, it underscores the importance of lipid modulation and encourages further exploration of tolcapone-associated mechanisms in the central nervous system (CNS).

Evaluation of the association COMT Val158Met variant and childhood trauma on aggression in Turkish SCZ patients

Childhood trauma is a serious form of stress that makes individuals more vulnerable to developing Schizophrenia (SCZ). Many studies have predicted the association between the catechol-O-methyltransferase (COMT) gene Val158Met variant and aggressive attack. We aimed to investigate the association the COMT variant and childhood trauma on aggression in Turkish SCZ patients This study included 89 patients diagnosed with SCZ. Childhood Trauma Questionnaire (CTS) and Overt Aggression Scale (OAS) were used to assess childhood trauma and aggression. COMT Val158Met variant was analyzed by PCR-RFLP method from isolated DNAs. There was no statistically significant difference in comparing the COMT genotype distribution and clinical characteristics including suicide attempts, self-destructive behavior, crime history, substance, alcohol and tobacco use. When we evaluate Spearman’s rank correlation coefficients between CTQ and OAS, the correlation between the OAS and CTQ scores of the patients was statistically significant except for the sexual abuse subgroup of the CTQ. In the univariate logistic regression analysis, in which the dichotomized OAS score was accepted as the dependent variable, it was found that age, suicide attempt, substance abuse, and CTQ total score significantly predicted the higher OAS scores. In the multivariate logistic regression analysis, which included the variables that predicted OAS significantly, age, suicide attempt, and total CTQ score were determined as independent variables predicting OAS. Because of the phenotypic complexity in SCZ, it is difficult to draw strong conclusions about COMT and to highlight a definitive relationship. Larger-scale studies are needed to examine the multifactorial inheritance pattern of schizophrenia in different dimensions.

Comparative metabolism of aschantin in human and animal hepatocytes.

Aschantin, a tetrahydrofurofuran lignan with a 1,3-benzodioxole group derived from Flos Magnoliae, exhibits antioxidant, anti-inflammatory, cytotoxic, and antimicrobial activities. This study compared the metabolic profiles of aschantin in human, dog, mouse, and rat hepatocytes using liquid chromatography-high-resolution mass spectrometry. The hepatic extraction ratio of aschantin among the four species was 0.46-0.77, suggesting that it undergoes a moderate-to-extensive degree of hepatic metabolism. Hepatocyte incubation of aschantin produced 4 phase 1 metabolites, including aschantin catechol (M1), O-desmethylaschantin (M2 and M3), and hydroxyaschantin (M4), and 14 phase 2 metabolites, including O-methyl-M1 (M5 and M6) via catechol O-methyltransferase (COMT), six glucuronides of M1, M2, M3, M5, and M6, and six sulfates of M1, M2, M3, M5, and M6. Enzyme kinetic studies using aschantin revealed that the production of M1, a major metabolite, via O-demethylenation is catalyzed by cytochrome 2C8 (CYP2C8), CYP2C9, CYP2C19, CYP3A4, and CYP3A5 enzymes; the formation of M2 (O-desmethylaschantin) is catalyzed by CYP2C9 and CYP2C19; and the formation of M4 is catalyzed by CYP3A4 enzyme. Two glutathione (GSH) conjugates of M1 were identified after incubation of aschantin with human and animal liver microsomes in the presence of nicotinamide adenine dinucleotide phosphate and GSH, but they were not detected in the hepatocytes of all species. In conclusion, aschantin is extensively metabolized, producing 18 metabolites in human and animal hepatocytes catalyzed by CYP, COMT, UDP-glucuronosyltransferase, and sulfotransferase. These results can help in clarifying the involvement of metabolizing enzymes in the pharmacokinetics and drug interactions of aschantin and in elucidating GSH conjugation associated with the reactive intermediate formed from M1 (aschantin catechol).

Neuroprotective Potential of Polydatin in Combating Parkinson’s Disease through the Inhibition of Monoamine Oxidase-B and Catechol-o-Methyl Transferase

Aims: This study aims to deduce the plausible contribution of polydatin in dopamine replenishment and dopaminergic neuroprotection to unveil its potential as a drug candidate for PD. Background: Available therapies for the management of dopaminergic degradation in Parkinson’s disease (PD) provide only symptomatic relief and are associated with various adverse effects. Levodopa (L-DOPA) is an age-old therapy in the treatment paradigm of PD, either used as mono-therapy or in combination with the inhibitors of the dopamine catabolising enzymes monoamine oxidase-B (MAO-B) and catechol O-methyltransferase (COMT) for replenishing the levels of the neurotransmitter. The discovery of plant-based novel drug therapies would help to target multiple pathways underlying the disease pathogenesis and are associated with minimal side effects. Polydatin, the precursor of resveratrol, has been explored recently to possess neuroprotective efficacy, however, the molecular mechanisms that underlie the Parkinsonism-associated neurobehavioral recovery as well as the neurorescue potential of polydatin has not been illustrated yet. Objective: The present study aimed to unveil the role of polydatin in dopamine upregulation in PD, by determining its dual inhibitory potential on the enzymes responsible for its breakdown, MAO-B and COMT. The study further aimed to elucidate the role of this molecule in regulating the enzymatic activity of Cytosolic Phospholipase A2 (cPLA2), the crucial enzyme underlying several pathogenic pathways leading to neurodegeneration. Methods: Molecular docking simulation of polydatin with the dopamine catabolizing enzymes MAO-B and COMT, as well as cPLA2, along with their respective known inhibitors was performed using the Molegro Virtual Docker (MVD) 2.1 package. Results: In-silico analyses revealed that polydatin could significantly inhibit the activities of this dopamine catabolizing enzyme, MAO-B, and COMT with comparable docking scores and more numbers of hydrogen bonds, and weaker interactions as that of their respective available synthetic inhibitors. Moreover, it was found that polydatin could regulate the activity of cPLA2 comparable to its known inhibitors. Conclusion: Polydatin exhibited efficacy as a potent dopamine replenishing agent by inhibiting its metabolizing enzymes as well as found to have efficacy against neuroinflammation, thereby highlighting the significance of designing novel phyto drugs for combating dopamine deficiency in PD.

Bioactive components and mechanisms of Pu-erh tea in improving levodopa metabolism in rats through COMT inhibition.

Catechol-O-methyltransferase (COMT) plays a central role in the metabolic inactivation of endogenous neurotransmitters and xenobiotic drugs and hormones having catecholic structures. Its inhibitors are used in clinical practice to treat Parkinson's disease. In this study, a fluorescence-based visualization inhibitor screening method was developed to assess the inhibition activity on COMT both in vitro and in living cells. Following the screening of 94 natural products, Pu-erh tea extract exhibited the most potent inhibitory effect on COMT with an IC50 value of 0.34 μg mL-1. In vivo experiments revealed that Pu-erh tea extract substantially hindered COMT-mediated levodopa metabolism in rats, resulting in a significant increase in levodopa levels and a notable decrease in 3-O-methyldopa in plasma. Subsequently, the chemical components of Pu-erh tea were analyzed using UHPLC-Q-Exactive Orbitrap HRMS, identifying 24 major components. Among them, epigallocatechin gallate, gallocatechin gallate, epicatechin gallate, and catechin gallate exhibited potent inhibition of COMT activity with IC50 values from 93.7 nM to 125.8 nM and were the main bioactive constituents in Pu-erh tea responsible for its COMT inhibition effect. Inhibition kinetics analyses and docking simulations revealed that these compounds competitively inhibit COMT-mediated O-methylation at the catechol site. Overall, this study not only explained how Pu-erh tea catechins inhibit COMT, suggesting Pu-erh tea as a potential dietary intervention for Parkinson's disease, but also introduced a new strategy for discovering COMT inhibitors more effectively.

Udruženost polimorfizama gena za katehol-Ometiltransferazu sa terapijskim odgovorom i komplikacijama izazvanim levodopom kod Parkinsonove bolesti - rezime sadašnjih saznanja

Catechol-O-methyltransferase (COMT) is one of the cardinal enzymes in the degradation of catecholamines and levodopa. Genetic variants of the COMT gene may affect COMT enzyme activity. The most examined COMT gene polymorphism is the nonsynonymous single nucleotide polymorphism (SNP) in exon 4 (Val108/158Met; rs4680). This highly functional polymorphism is responsible for fourfold variations in enzyme activity and Dopamine catabolism. Recent data suggested that even synonymous SNPs of the COMT gene can lead to changes in enzyme activity. Genetically determined COMT activity can affect an individual's response to levodopa therapy and carries the risk of complications from prolonged levodopa use in Parkinson's disease (PD) patients. Identifying at-risk individuals through genetic susceptibility markers could help to prevent the development of levodopa-induced complications in PD.

Repurposing Entacapone, a Catechol-O-Methyl Transferase Inhibitor, for Alcohol Use Disorder: A Combined Morgan Fingerprint and Docking Approach

This study investigates the potential of repurposing Entacapone, a known catechol-O-methyl transferase (COMT) inhibitor, for the treatment of Alcohol Use Disorder (AUD) using an integrated approach that combines Morgan Fingerprint analysis and molecular docking studies. Entacapone, originally approved for managing Parkinson’s disease, was identified as a candidate through ligand-based virtual screening on the DrugRep platform. The screening revealed a strong binding affinity of Entacapone to aldehyde dehydrogenase (ALDH), with a docking score of -8.3, suggesting its potential to inhibit this enzyme, similar to the mechanism of action seen with Disulfiram, a commonly used AUD medication. Molecular docking studies further highlighted key interactions between Entacapone and critical residues in ALDH, providing a structural basis for its repurposing in AUD therapy. Validation metrics from PDB-REDO showed notable improvements in model quality, with reductions in the R-free value from 0.2772 to 0.2490, and enhancements in bond angle RMS Zscores and Ramachandran plot normality, further supporting the robustness of the docking results. This study underscores the feasibility of using Entacapone as a potential therapeutic agent for AUD and highlights the utility of combining ligand-based screening with molecular docking in drug repurposing. The findings pave the way for further experimental validation and potential clinical applications for AUD treatment, especially in patients seeking alternative therapeutic options.

Exploring the Viability of Neurobic Exercises as an Intervention for Cognitive Impairment: A Literature Review

Aim: To investigate the viability of implementing neurobic exercise interventions among adults diagnosed with Mild Cognitive Impairment (MCI). Materials and Methods: A comprehensive search of electronic databases PubMed, Google Scholar, Medline, was done for relevant studies, including randomised controlled trials, observational studies. Inclusion criteria were both male and female with cognitive impairment, implementation of neurobic programme and their follow ups. A total of four articles were synthesised out of 12, for the review based on the inclusion criteria. Results: All the four studies yielded positive results. Firstly, use of neurobic exercises exhibited a significant decrease in Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) relative change scores, indicating cognitive decline improvement, and significantly higher Catechol-O-methyltransferase (COMT) relative change scores, reflecting enhanced cognitive performance at 3rd and 6th weeks. Secondly, serum Brain-derived Neurotrophic Factor (BDNF) level in the neurobic group was slightly higher than pretest. There was change in Montreal Cognitive Assessment (MoCA) scale in post treatment experimental group as compared to conventional group. Participants expressed high satisfaction with the activities and perceived the intervention as helpful. Conclusion: The implementation of neurobic exercise interventions proved to be both feasible and was well-received by people with cognitive impairment. It also proved to improve quality of life. Neurobic exercises suggest future research avenues demonstrating a forward looking approach to address existing research gaps.

The Catechol‐O‐Methyltransferase (COMT) Val158Met Polymorphism Is Associated with Oxycodone Requirements, Adverse Effects, and Pain Sensitivity in Cancer Patients

The Catechol‐O‐Methyltransferase (COMT) Val158Met Polymorphism Is Associated with Oxycodone Requirements, Adverse Effects, and Pain Sensitivity in Cancer Patients

A newly synthesized flavone avoids COMT-catalyzed methylation and mitigates myocardial ischemia/reperfusion injury in H9C2 cells via JNK and P38 pathways.

Luteolin is a flavone that provides defense against myocardial ischemia/reperfusion (I/R) injury. However, this compound is subjected to methylation mediated by catechol-O-methyltransferase (COMT), thus influencing its pharmacological effect. To synthesize a new flavone from luteolin that avoids COMT-catalyzed methylation and find out the protective mechanism of LUA in myocardial I/R injury. Luteolin and 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH) were used to synthesize the new flavone known as LUAAPH-1 (LUA). Then, the myocardial ischemia/reperfusion injury cell model was established using H9c2 cells to detect the effect in myocardial ischemia/reperfusion regulation and to identify the underlying mechanism. Pretreatment with LUA (20 μmol/l) substantially increased cell viability while reducing cell apoptosis rate and caspase-3 expression induced by I/R, and the protective effect of LUA on cell viability was stronger than diosmetin, which is the major methylated metabolite of luteolin. In addition, intracellular reactive oxygen species (ROS) production and calcium accumulation were both inhibited by LUA. Furthermore, we identified that LUA markedly relieved the promotive effects of I/R stimulation upon JNK and p38 phosphorylation. LUT pretreatment conveys significant cardioprotective effects after myocardial I/R injury, and JNK and p38 MAPK signaling pathway may be involved.

Genes of cancer-related fatigue: a scoping review.

Cancer-related fatigue (CRF) is a prevalent adverse effect experienced by cancer patients while receiving and after treatment, impacting as many as 90% of individuals. Although CRF is common, the genetic processes responsible for it and their influence on individual vulnerability are not well understood and are still being investigated. The primary objective of this scoping review is to identify and assess genes linked to the vulnerability and severity of CRF. This will help us better understand the genetic factors involved and assist in developing targeted nursing treatments in clinical settings. This review followed the PRISMA guidelines. A comprehensive search was performed in databases, such as PubMed, EMBASE, Web of Science, Cochrane Library, SinoMed, CNKI, and VIP, encompassing genetic association studies on CRF published up to February 25, 2024. The JBI Critical Appraisal Tools were used to assess the quality of observational studies. This evaluation encompassed a comprehensive analysis of 14 studies that involved 3,254 patients. The results indicate strong connections between CRF and various inflammatory cytokines (IL-4, IL-6, IL-8, IL-10, IL-1β), tumor necrosis factor-alpha (TNF-α), catechol-O-methyltransferase (COMT), and circadian rhythm genes (CLOCK, PER). This scoping review emphasizes the significant genetic factor in CRF, with multiple genes showing distinct effects on cancer fatigue symptoms. Identifying these genes enhances our comprehension of CRF and unveils novel avenues for cancer treatment approaches. Future research should prioritize conducting cohort studies to monitor alterations in gene expression pre- and post-treatment, hence improving individualized medicinal strategies in oncology.

Psychological and genetic characteristics and strategies of students’ digital behavior in the context of the formation of the digital ecosystem

The objective of our study was to investigate the attributes of the cognitive, affective, and value-semantic domains, along with genetic predictors, that influence the digital behavior of young individuals. The study involved 91 people (33 males and 58 females) aged 18 to 25 years (Russian Federation). In order to measure digital behavior the questioner “Strategies of informational behavior” (SIP) was used. In order to study the cognitive, affective and value-semantic characteristics, the following tests were used: the Test of Life-Sense Orientations, the Buss-Durkee Hostility Inventory, the Gottschaldt Figures Test (a measure of embedded figures perception), and a method for assessing thinking style. Genotyping was use to examine polymorphisms of the COMT, DRD2, and BDNF genes. Our findings demonstrate statistically significant associations between constructive and destructive digital behaviors and specific facets of the participants’ cognitive, affective, and value-semantic domains, as well as distinct aspects of dopaminergic system functionality.

Body index mass not associated with DRD4, DAT1, BDNF, and COMT gene polymorphisms in young adults without depression or anxiety disorders

Body index mass not associated with DRD4, DAT1, BDNF, and COMT gene polymorphisms in young adults without depression or anxiety disorders

Unraveling Catechol-O-Methyltransferase rs4680 SNP's Role in Patients' Response to Tramadol and Its Adverse Effects: A Pharmacogenetics Insight into Postoperative Pain Management.

Effective postoperative pain management is essential for patient well-being and an efficient healthcare system. Variations in the Catechol O-Methyltransferase (COMT) gene, specifically rs4680, play a crucial role in pain perception and opioid response. This study seeks to elucidate the impact of rs4680 polymorphism on tramadol efficacy and adverse reactions in post-surgical patients. We performed an uncontrolled cohort pharmacogenetics study in which participants underwent postoperative tramadol administration. The frequencies of rs4680 alleles were determined and the association between rs4680 genotypes and the efficacy of tramadol analgesic as pain relief, measured by the Numeric Rating Scale (NRS), was analyzed. Secondary outcomes included tramadol-induced sedation levels, opioid-induced nausea and vomiting, and other adverse effects of tramadol. Data analysis, using IBM SPSS Statistics 23, focused on pain and side effect differences across genotypes, with statistical significance set to p ≤ 0.05. The COMT (rs4680) genotype distribution exhibited a 'G' allele frequency of 41.5% and an 'A' allele frequency of 58.5%, with the AA genotype present in 44% of individuals, adhering to the Hardy-Weinberg equilibrium (p = 0.788). Patients with the AA genotype reported lower pain scores post-tramadol administration across all times examined (p < 0.001), but also experienced statistically significant (p < 0.001) higher incidences of tramadol-induced nausea, vomiting, and sedation. However, GG genotype individuals experienced poor pain relief from tramadol, requiring more supplemental analgesia. These significant findings underscore the critical role of COMT rs4680 polymorphism in response to tramadol and the necessity of a personalized approach to postoperative pain management.