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Regression analysis of the association between drug addiction features and candidate SNPs of OPRM1 gene (Continued)
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Background: Like other complex diseases including drug addiction, genetic factors can interfere with the disease. In this study, three opioid genes (OPRM1, OPRD1, and OPRK1) were examined for an association with drug addiction among Jordanian males.
Methods: The study involved 498 addicts, in addition to 496 healthy controls and all from Arab des...
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This review article offers an outlook on the use of opioids as therapeutics for treating several diseases, including cancer and non-cancer pain, and focuses the analysis on the opportunity to target opioid receptors for treating opioid use disorder (OUD), drug withdrawal, and addiction. Unfortunately, as has been well established, the use of opioid...
Citations
... For example, research has focused on the Serotonin Transporter Gene (SLC6A4/5-HTT) [27,28] and its polymorphic variant 5-HTTLPR, which have been implicated in regulating serotonin and associated with substance use behaviors. Other studies have examined the DRD4 exon III gene [29], which is linked to dopamine regulation and reward pathways, and the Mu opioid receptor gene (OPRM1) [30][31][32], known for its role in the body's response to opioids and its potential influence on addiction susceptibility. This study aimed to investigate whether specific polymorphisms within three nicotinic receptor genes-CHRNA5, CHRNA3, and CHRNB4-are associated with an increased risk of substance use disorder among Jordanian males. ...
Background
Substance use disorder (SUD) is a complex illness that can be attributed to the interaction between environmental and genetic factors. The nicotinic receptor gene cluster on chromosome 15 has a plausible association with SUD, particularly with nicotine dependence.
Methods
This study investigated 15 SNPs within the CHRNA5, CHRNA3, and CHRNB4 genes. Sequencing was used for genotyping 495 Jordanian males with SUD and 497 controls matched for age, gender, and descent.
Results
Our findings revealed that none of the tested alleles or genotypes were correlated with SUD. However, our analysis suggests that the route of substance use was linked to rs1051730 (P value = 0.04), rs8040868 (P value = 0.01) of CHRNA3, and rs16969968 (P value = 0.03) of CHRNA5. Additionally, a correlation was identified between rs3813567 of the CHRNB4 gene and the age at substance use onset (P value = 0.04).
Conclusions
Variants in CHRNA5, CHRNA3, and CHRNB4 may interact with SUD features that can influence the development and progression of the disorder among Jordanians.
... Aldehyde dehydrogenase 2 (ALDH2) is a key enzyme in the oxidation process of acetaldehyde to acetate, which has been associated with an increased risk of drug addiction [10]. The OPRM1 gene is also associated with drug addiction [11], and OPRM1 rs1799971 was shown to be a genetic risk factor for drug addiction among Jordanian males. rs2133896 in ANKS1B is associated with its gene expression and with reduced the gray matter in the left calcarine and white matter in the right superior longitudinal fasciculus in individuals with heroin dependence [12]. ...
Background
Drug addiction is a serious problem worldwide and is influenced by genetic factors. The present study aimed to investigate the association between genetics and drug addiction among Han Chinese.
Methods
A total of 1000 Chinese users of illicit drugs and 9693 healthy controls were enrolled and underwent single nucleotide polymorphism (SNP)-based and haplotype-based association analyses via whole-genome genotyping.
Results
Both single-SNP and haplotype tests revealed associations between illicit drug use and several immune-related genes in the major histocompatibility complex (MHC) region (SNP association: log10BF = 15.135, p = 1.054e-18; haplotype association: log10BF = 20.925, p = 2.065e-24). These genes may affect the risk of drug addiction via modulation of the neuroimmune system. The single-SNP test exclusively reported genome-wide significant associations between rs3782886 (SNP association: log10BF = 8.726, p = 4.842e-11) in BRAP and rs671 (SNP association: log10BF = 7.406, p = 9.333e-10) in ALDH2 and drug addiction. The haplotype test exclusively reported a genome-wide significant association (haplotype association: log10BF = 7.607, p = 3.342e-11) between a region with allelic heterogeneity on chromosome 22 and drug addiction, which may be involved in the pathway of vitamin B12 transport and metabolism, indicating a causal link between lower vitamin B12 levels and methamphetamine addiction.
Conclusions
These findings provide new insights into risk-modeling and the prevention and treatment of methamphetamine and heroin dependence, which may further contribute to potential novel therapeutic approaches.
... Further, cocaine dependence was shown by Pavarin and Fioritti as a major risk factor for suicide in Italy [37]. Drug dependence is generally defined as a persistent, strong, and uncontrollable tendency to take substances and characterized by physical, social, physiological, and psychological dysfunction [38,39]. In a study performed by AL-Eitan et al. on 498 addicts, drug addiction was shown to be a significant driving factor for suicide [40]. ...
Suicide is a major global public health problem, with profound implications for individuals, families, and communities. In the United Kingdom (UK), despite efforts to detect and manage suicidal ideas, suicide rates persist, especially among middle-aged men and women, particularly those aged 45 to 54 years. Recent global challenges, such as the COVID-19 pandemic, climate change, conflict, and the environmental crisis, have raised concerns about an increase in suicide rates, particularly among young people. As a result, a population-wide preventive approach based on evidence is imperative to mitigate the projected increase in suicides. To evaluate the effectiveness of suicide prevention strategies, there is a need for an objective and universally accepted risk assessment approach that does not currently exist. This review examines the current landscape of suicide prevention in the United Kingdom and evaluates the strengths and limitations of existing suicide risk assessments tools. The current suicide prevention tools used, including machine learning and mobile applications are discussed. Also, the epidemiological trends in the various regions of the UK, risk factors including age, sex, and socio-economic status are assessed to provide context. Through this discourse, we hope to provide valuable insight for clinicians, researchers, and policy makers about the current landscape of suicide, especially within the United Kingdom, while presenting recommendations regarding areas that require further research and improvement. Accordingly, suicide prevention is and will continue to be a major focus of both the national health service and research in the UK in the strive to reduce the rate of suicide across all regions. Indeed, headways have been made in the use of technology in preventing suicide both locally and globally. However, research should in the future investigate the value of personalized interventions tailored to the various risk factors of suicide and based on appropriate screening and assessment tools.
... It has also been reported to inhibit dependence on the psychostimulant methamphetamine, which has a different mechanism of action from opioids, and is being studied for clinical use [18,19]. Genetic polymorphisms of opioid receptor genes have been reported to be associated with addiction to opioids and other addictive substances [20][21][22]. These findings suggest that actions on the endogenous opioid system may be a common mechanism of substance use disorders. ...
Although opioids are widely used to treat moderate to severe pain, opioid addiction and the opioid overdose epidemic are becoming more serious. Although opioid receptor antagonists/partial agonists, such as naltrexone and buprenorphine, have relatively low selectivity for the μ-opioid receptor (MOP), they have been used for the management of opioid use disorder. The utility of highly selective MOP antagonists remains to be evaluated. Here, we biologically and pharmacologically evaluated a novel nonpeptide ligand, UD-030, as a selective MOP antagonist. UD-030 had more than 100-fold higher binding affinity for the human MOP (Ki = 3.1 nM) than for δ-opioid, κ-opioid, and nociceptin receptors (Ki = 1800, 460, and 1800 nM, respectively) in competitive binding assays. The [35S]-GTPγS binding assay showed that UD-030 acts as a selective MOP full antagonist. The oral administration of UD-030 dose-dependently suppressed the acquisition and expression of morphine-induced conditioned place preference in C57BL/6J mice, and its effects were comparable to naltrexone. These results indicate the UD-030 may be a new candidate for the treatment of opioid use disorder, with characteristics that differ from traditional medications that are in clinical use.
... Determining how genetic variables contribute to the etiology of addiction may enhance patient responsiveness to care and aid in disease prevention. By identifying the genes that are essential for neuroadaptation, both genome-wide approaches and candidate gene studies have been used to investigate the fundamental significance of the genetic component of drug addiction [22]. There are multiple studies that support the link between genetic polymorphism and substance abuse. ...
... The study found that the OPRM1 gene's rs1799971 was associated with drug addiction, for both alleles and genotypes. Further, the age of addicted individuals, their smoking, and their marital status may be associated with the risk of developing a drug addiction, along with genetic variants in the OPRM1, OPRD1, and OPRK1 genes [22]. Another study on the brain-derived neurotrophic factor (BDNF), a member of the neurotrophic factor family, shows that it may be involved in the mechanisms behind substance misuse, according to data from animal research and genetic tests on humans. ...
... There are unfortunately no statistics on the population prevalence of dinucleotide or a variable number of tandem repeats [24]. Almost all previous studies suggest a significant link between genetic polymorphism and drug abuse, with a wide variety of gene involvements [22][23][24]. ...
Substance use disorder and the availability of certain over-the-counter drugs are worldwide issues that affect many individuals, both mentally and physically. As a result, the frequent use of this substance can lead to substance abuse. This phenomenon is also becoming more prevalent with time, and it does not differentiate between genders, ages, races, or religions. This review aimed to provide an overview of studies related to substance abuse, the individuals who tend to abuse these substances, and their risk factors. We also aimed to discuss, identify, and analyze the factors that increase the risk of substance abuse among young adults. We performed a thorough search for related studies using PubMed to provide a comprehensive review of the risk factors and side effects experienced by young adults. The selected indexing terms included "substance abuse,""risk factors," and "personality traits," among others. Information was gathered from relevant peer-reviewed publications, and thereafter refined, and summarized.
... The brain's reward system has a great impact on behavioral control and plays an important role in the pathophysiology of addictive behaviors. Dopaminergic and serotonergic neurotransmitter systems involved in these reward pathways are at the center of attention in candidate gene studies of substance abuse, non-substance addictions, and various risk behavior-related traits such as novelty seeking, impulsivity, or aggressive behavior [40,41]. Functional neuroimaging studies have shown that cocaine, money, and beauty similarly energize the reward circuitry of the brain [42], implying that similar neurobiological pathways are stimulated in the brain regardless of the object of the addiction [43]. ...
Reward Deficiency Syndrome (RDS) is defined as a breakdown of reward neurotransmission that results in a wide range of addictive, compulsive, and impulsive behaviors. RDS is caused by a combination of environmental (epigenetic) influences and DNA-based (genetic) neurotransmission deficits that interfere with the normal satisfaction of human physiological drives (i.e., food, water, and sex). An essential feature of RDS is the lack of integration between perception, cognition, and emotions that occurs because of (1) significant dopaminergic surges in motivation, reward, and learning centers causing neuroplasticity in the striato-thalamic-frontal cortical loop; (2) hypo-functionality of the excitatory glutamatergic afferents from the amygdala–hippocampus complex. A large volume of literature regarding the known neurogenetic and psychological underpinnings of RDS has revealed a significant risk of dopaminergic gene polymorphic allele overlap between cohorts of depression and subsets of schizophrenia. The suggestion is that instead of alcohol, opioids, gambling disorders, etc. being endophenotypes, the true phenotype is RDS. Additionally, reward deficiency can result from depleted or hereditary hypodopaminergia, which can manifest as a variety of personality traits and mental/medical disorders that have been linked to genetic studies with dopamine-depleting alleles. The carrying of known DNA antecedents, including epigenetic insults, results in a life-long vulnerability to RDS conditions and addictive behaviors. Epigenetic repair of hypodopaminergia, the causative basis of addictive behaviors, may involve precision DNA-guided therapy achieved by combining the Genetic Addiction Risk Severity (GARS) test with a researched neutraceutical having a number of variant names, including KB220Z. This nutraceutical formulation with pro-dopamine regulatory capabilities has been studied and published in peer-reviewed journals, mostly from our laboratory. Finally, it is our opinion that RDS should be given an ICD code and deserves to be included in the DSM-VI because while the DSM features symptomology, it is equally important to feature etiological roots as portrayed in the RDS model.
... Chronic pain, which may be concurrent with anxiety, may be associated with neuroplastic changes in the amygdala, which may heighten the emotional and affective consequences of pain [63,64]. Opioid analgesics are highly effective in most cases against acute pain, but the desired effects mediated by the opioid receptor family may lead to craving, addiction, or dependence as a result of neurological changes [65][66][67][68]. Repetitive opioid use will thus increase the threshold for analgesic effects secondary to compensatory upregulation of vesicular calcium content while developing opioid tolerance, and it may decrease one's quality of life [55,69,70]. ...
The opioid epidemic is an ongoing public health crisis, and the United States health system is overwhelmed with increasing numbers of opioid-related overdoses. Methocinnamox (MCAM) is a novel mu opioid receptor antagonist with an extended duration of action. MCAM has potential to reduce the burden of the opioid epidemic by being used as an overdose rescue treatment and a long-term treatment for opioid use disorder (OUD). The currently available treatments for OUD include naloxone, naltrexone, and methadone. These treatments have certain limitations, which include short duration of action, patient non-compliance, and diversion. A narrative review was conducted using PubMed and Google Scholar databases covering the history of the opioid epidemic, pain receptors, current OUD treatments and the novel drug MCAM. MCAM could potentially be used as both a rescue and long-term treatment for opioid misuse. This is due to its pseudo-irreversible antagonism of the mu opioid receptor, abnormally long duration of action of nearly two weeks, and the possibility of using kappa or delta opioid receptor agonists for pain management during OUD treatment. MCAM's novel pharmacokinetic and pharmacodynamic properties open a new avenue for treating opioid misuse.
Background
The health and social consequences of substance/alcohol use disorders are harmful. Most of the individuals cannot stop using them due to more likely their genetic background. The current study aimed both to develop a novel PCR-RFLP method for genotyping of MAOA rs1465108 and to analyze the effect of MAOA rs1465108 on the risk of alcohol (AUD), opioid (OUD) or methamphetamine (MUD) use disorders and on the depressive and anxiety symptoms in a Turkish population.
Methods and results
A total of 353 individual with AUD (n = 154), OUD (n = 160) or MUD (n = 39) and 109 healthy subjects were included. The intensity of anxiety and depressive symptoms and craving and opioid withdrawal were measured by appropriate scales. Logistic regression analysis revealed no association between MAOA rs1465108 polymorphism and substance/alcohol use disorder (p > 0.05). Healthy subjects (3.0) had significantly lower levels of depressive symptoms than individuals with OUD (27.0), AUD (21.0) and MUD (25.5) groups. The severity of depressive symptoms was significantly higher in OUD as compared to AUD. There was a statistically significant difference between individuals with AUD, OUD and MUD in view of the average ages of first use (17, 19 and 20 years, respectively) (p < 0.05).
Conclusions
The results presented here do not support the hypothesis that MAOA rs1465108 is associated with substance/alcohol use disorders. The intensity of depressive symptoms could be changed according to the abused substance type. A novel PCR-RFLP was developed for genotyping of MAOA rs1465108 polymorphism, which could be a better option for laboratories without high technology equipment.
A high number of genome variants are associated with complex traits, mainly due to genome-wide association studies (GWAS). Using polygenic risk scores (PRSs) is a widely accepted method for calculating an individual’s complex trait prognosis using such data. Unlike monogenic traits, the practical implementation of complex traits by applying this method still falls behind. Calculating PRSs from all GWAS data has limited practical usability in behaviour traits due to statistical noise and the small effect size from a high number of genome variants involved. From a behaviour traits perspective, complex traits are explored using the concept of core genes from an omnigenic model, aiming to employ a simplified calculation version. Simplification may reduce the accuracy compared to a complete PRS encompassing all trait-associated variants. Integrating genome data with datasets from various disciplines, such as IT and psychology, could lead to better complex trait prediction. This review elucidates the significance of clear biological pathways in understanding behaviour traits. Specifically, it highlights the essential role of genes related to hormones, enzymes, and neurotransmitters as robust core genes in shaping these traits. Significant variations in core genes are prominently observed in behaviour traits such as stress response, impulsivity, and substance use.
