Implication of OPRM1 A118G Polymorphism in Opioids Addicts in Pakistan: In vitro and In silico Analysis

Ahmed, Madiha; Haq, İhsan Ul; Faisal, Muhammad; Waseem, Durdana; Taqi, Malik Mumtaz

doi:10.1007/s12031-018-1123-1

Cited by 23 publications

(15 citation statements)

References 58 publications

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“…The frequency of the A118G variant allele of 0.084 in healthy Turkish population established by this study places it with the European Caucasian populations, namely Swedish (6), Norwegian (23), and Hispanic (24) ( Table 5) in between the African American population at the lowest end of the range and Asian populations at the higher end (21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33).…”

Section: Discussionsupporting

confidence: 52%

The association between the OPRM1 A118G polymorphism and addiction in a Turkish population

Türkan

Karahalıl

Kadıoğlu

et al. 2019

Archives of Industrial Hygiene and Toxicology

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Susceptibility to addiction has a complex genetic basis that includes genes associated with the action and metabolism of drugs of abuse. One important gene in that respect is OPRM1, which codes for the μ-opioid receptor and has an important role in mediating the rewarding effects of addiction substances. The aim of our study was to assess the prevalence of the OPRM1 A118G polymorphism (rs1799971) in Turkish population and to investigate its association with opioid and other substance addiction. In addition, we examined the association of rs1799971 in addicted patients who were also diagnosed with psychiatric disorders. The study included 103 patients addicted to opioids, cocaine, ecstasy, alcohol, lysergic acid diethylamide (LSD), cannabis, and sedative/hypnotic substances and 83 healthy volunteers with similar demographic features as controls. rs1799971 polymorphisms were identified with the polymerase chain reaction restriction fragment length polymorphism method (PCR-RFLP). The genotype frequencies were significantly higher in the addicted patients than controls (32.0 % vs 16.9 %, respectively; p=0.027). The prevalence of the G allele was 16.1 % in the addicted group and 8.4 % in the control group (p=0.031). Our study confirmed the association between the rs1799971(G) allele frequency and opioid and other substance addiction, but not with psychiatric disorders.

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Section: Discussionsupporting

confidence: 52%

The association between the OPRM1 A118G polymorphism and addiction in a Turkish population

Türkan

Karahalıl

Kadıoğlu

et al. 2019

Archives of Industrial Hygiene and Toxicology

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“…CYP2D6 ultra-rapid metabolizers are more likely to experience adverse events with opioid treatment [58]. In the presence of opioids, RARA (p best_SNP = 0.02) forms a complex with RXRA, which activates the mu-opioid receptor and modulates drug-seeking behaviors [59]. Some mutations in the vitamin D receptor gene (VDR, p gene = 0.04, p best_SNP = 0.001) have been associated with impulsivity in the context of alcohol dependence [60].…”

Section: Discussionmentioning

confidence: 99%

Genome-Wide Association Study of Opioid Cessation

Cox

Sherva

Lunetta

et al. 2020

JCM

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The United States is experiencing an epidemic of opioid use disorder (OUD) and overdose-related deaths. However, the genetic basis for the ability to discontinue opioid use has not been investigated. We performed a genome-wide association study (GWAS) of opioid cessation (defined as abstinence from illicit opioids for >1 year or <6 months before the interview date) in 1130 African American (AA) and 2919 European ancestry (EA) participants recruited for genetic studies of substance use disorders and who met lifetime Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria for OUD. Association tests performed separately within each ethnic group were combined by meta-analysis with results obtained from the Comorbidity and Trauma Study. Although there were no genome-wide significant associations, we found suggestive associations with nine independent loci, including three which are biologically relevant: rs4740988 in PTPRD (pAA + EA = 2.24 × 10−6), rs36098404 in MYOM2 (pEA = 2.24 × 10−6), and rs592026 in SNAP25-AS1 (pEA = 6.53 × 10−6). Significant pathways identified in persons of European ancestry (EA) are related to vitamin D metabolism (p = 3.79 × 10−2) and fibroblast growth factor (FGF) signaling (p = 2.39 × 10−2). UK Biobank traits including smoking and drinking cessation and chronic back pain were significantly associated with opioid cessation using GWAS-derived polygenic risk scores. These results provide evidence for genetic influences on opioid cessation, suggest genetic overlap with other relevant traits, and may indicate potential novel therapeutic targets for OUD.

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“…As such, genetic variations of OPRM1 may be the key to identifying patient dependence liability. Multiple articles have provided evidence that the A118G SNP is associated with drug dependence (Ahmed et al, 2018; Kapur et al, 2007; Tan et al, 2003). However, there are also studies that report no association (Kong et al, 2017).…”

Section: Opioid Pharmacodynamicsmentioning

confidence: 99%

The pharmacogenetics of opioid treatment for pain management

et al. 2020

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Background: Opioids are widely used as an analgesic for the treatment of moderate to severe pain. However, there are interindividual variabilities in opioid response. Current evidence suggests that these variabilities can be attributed to single nucleotide polymorphisms in genes involved in opioid pharmacodynamics and pharmacokinetics. Knowledge of these genetic factors through pharamacogenetic (PGx) testing can help clinicians to more consistently prescribe opioids that can provide patients with maximal clinical benefit and minimal risk of adverse effects. Aim: The research outlined in this literature review identifies variants involved in opioid PGx, which may be an important tool to achieving the goal of personalized pain management. Results: Cytochrome P450 ( CYP) 2D6, CYP3A4, CYP3A5, catechol-o-methyltransferase ( COMT), adenosine triphosphate binding cassette transporter B1 ( ABCB1), opioid receptor mu 1 ( OPRM1), and opioid receptor delta 1 ( OPRD1) are all important genes involved in opioid drug response, side effect profile and risk of dependence; these are important genetic factors that should be included in potential opioid PGx tests for pain management. Conclusions: Employing a PGx-guided strategy for prescribing opioids can improve response rate, reduce side effects and increase adherence to treatment plans for pain; more research is needed to explore opioid-related PGx factors for the development and validation of an opioid genetic panel. Optimal prescriptions could also provide healthcare payers with beneficial savings, while reducing the risk of propagating the current opioid crisis.

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Implication of OPRM1 A118G Polymorphism in Opioids Addicts in Pakistan: In vitro and In silico Analysis

Cited by 23 publications

References 58 publications

The association between the OPRM1 A118G polymorphism and addiction in a Turkish population

The association between the OPRM1 A118G polymorphism and addiction in a Turkish population

Genome-Wide Association Study of Opioid Cessation

The pharmacogenetics of opioid treatment for pain management

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