The Association of Genetic Polymorphisms in the κ-Opioid Receptor 1 Gene With Body Weight, Alcohol Use, and Withdrawal Symptoms in Patients With Methadone Maintenance

Wang, Sheng-Chang; Tsou, Hsiao‐Hui; Chung, Ren‐Hua; Chang, Yao-Sheng; Fang, Chiu‐Ping; Chen, Chia‐Hui; Ho, Ing-Kang; Kuo, Hsin‐Wei; Liu, Shu Chih; Shih, Yu-Huei; Wu, Hsiao-Yu; Huang, Bo-Hau; Lin, Keh‐Ming; Chen, Andrew C. H.; Liu, Yuli

doi:10.1097/jcp.0000000000000082

Cited by 30 publications

(19 citation statements)

References 33 publications

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“…This variant has previously been reported to be part of a risk haplotype accounting for higher alcohol use and withdrawal symptoms in patients on methadone maintenance. 34 However, in another study, no association was found with heroin and alcohol addiction. 35 Interestingly, a recent randomised, placebo-controlled clinical trial showed that the opioid receptor antagonist naltrexone decreases ICD symptom severity in patients with PD with ICD.…”

Section: Discussionmentioning

confidence: 90%

Clinical-genetic model predicts incident impulse control disorders in Parkinson's disease

Kraemmer

Smith

Weintraub

et al. 2016

J Neurol Neurosurg Psychiatry

101

121

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Objectives Impulse control disorders (ICD) are commonly associated with dopamine replacement therapy (DRT) in patients with Parkinson’s disease (PD). Our aims were to estimate ICD heritability and to predict ICD by a candidate genetic multivariable panel in patients with PD. Methods Data from de novo patients with PD, drug-naïve and free of ICD behaviour at baseline, were obtained from the Parkinson’s Progression Markers Initiative cohort. Incident ICD behaviour was defined as positive score on the Questionnaire for Impulsive-Compulsive Disorders in PD. ICD heritability was estimated by restricted maximum likelihood analysis on whole exome sequencing data. 13 candidate variants were selected from the DRD2, DRD3, DAT1, COMT, DDC, GRIN2B, ADRA2C, SERT, TPH2, HTR2A, OPRK1 and OPRM1 genes. ICD prediction was evaluated by the area under the curve (AUC) of receiver operating characteristic (ROC) curves. Results Among 276 patients with PD included in the analysis, 86% started DRT, 40% were on dopamine agonists (DA), 19% reported incident ICD behaviour during follow-up. We found heritability of this symptom to be 57%. Adding genotypes from the 13 candidate variants significantly increased ICD predictability (AUC=76%, 95% CI (70% to 83%)) compared to prediction based on clinical variables only (AUC=65%, 95% CI (58% to 73%), p=0.002). The clinical-genetic prediction model reached highest accuracy in patients initiating DA therapy (AUC=87%, 95% CI (80% to 93%)). OPRK1, HTR2A and DDC genotypes were the strongest genetic predictive factors. Conclusions Our results show that adding a candidate genetic panel increases ICD predictability, suggesting potential for developing clinical-genetic models to identify patients with PD at increased risk of ICD development and guide DRT management.

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Section: Discussionmentioning

confidence: 90%

Clinical-genetic model predicts incident impulse control disorders in Parkinson's disease

Kraemmer

Smith

Weintraub

et al. 2016

J Neurol Neurosurg Psychiatry

101

121

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“…Wang et al [66] reported that a kappa-opioid receptor 1 gene polymorphism is associated with alcohol use, among other things. …”

Section: Clinical Correlates Of Aud In Opioid Dependencementioning

confidence: 99%

Alcohol Use Disorders in Opioid Maintenance Therapy: Prevalence, Clinical Correlates and Treatment

Soyka¹

2014

Eur Addict Res

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Maintenance therapy with methadone or buprenorphine is an established and first-line treatment for opioid dependence. Clinical studies indicate that about a third of patients in opioid maintenance therapy show increased alcohol consumption and alcohol use disorders. Comorbid alcohol use disorders have been identified as a risk factor for clinical outcome and can cause poor physical and mental health, including liver disorders, noncompliance, social deterioration and increased mortality risk. The effects of opioid maintenance therapy on alcohol consumption are controversial and no clear pattern has emerged. Most studies have not found a change in alcohol use after initiation of maintenance therapy. Methadone and buprenorphine appear to carry little risk of liver toxicity, but further research on this topic is required. Recent data indicate that brief intervention strategies may help reduce alcohol intake, but the existing evidence is still limited. This review discusses further clinical implications of alcohol use disorders in opioid dependence.

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“…OPRK1 is critical in drug addiction, and OPRK1 agonists have inhibitory effects on addictions to alcohol, cocaine and opiate (28). Furthermore, several genetic variants of OPRK1 have been associated with heroin addiction (8,29,30). Previous studies have indicated that heritable factors may be important in addictive behavior (8,31), and suggest that higher levels of OPRK1 promoter methylation may be associated with heroin addiction.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, several genetic variants of OPRK1 have been associated with heroin addiction (8,29,30). Previous studies have indicated that heritable factors may be important in addictive behavior (8,31), and suggest that higher levels of OPRK1 promoter methylation may be associated with heroin addiction. The results of the present study indicate that OPRK1 promoter methylation affects the propensity of individuals to exhibit addictive behaviors.…”

Section: Discussionmentioning

confidence: 99%

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Hypermethylation of the κ1 opioid receptor promoter in Chinese heroin and methamphetamine addicts

Liu

et al. 2018

Exp Ther Med

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Heroin and methamphetamine (METH) addiction continues to be a major social, economic and therapeutic problem worldwide. The opioid pathway may mediate the effects of addictive drugs. However, the potential correlation between the κ1 opioid receptor (OPRK1) and drug addiction has not yet been characterized. The aim of the present study was to investigate the potential association between methylation of the OPRK1 promoter and substance abuse. Bisulfite pyrosequencing technology was used to determine the levels of OPRK1 promoter methylation in 60 drug abusers (30 heroin and 30 METH addicts) and 52 controls, observed to exhibit no significant differences in age or gender. The results indicated that levels of OPRK1 promoter methylation were significantly higher in drug addicts when compared with controls (P=2.43×10−4). Significant correlations between OPRK1 promoter methylation and the length and frequency of drug use were also observed in male heroin addicts (length: r=0.661, P=0.007; frequency: r=−0.684, P=0.005). In addition, a luciferase reporter gene assay indicated that the OPRK1 promoter fragment was able to regulate gene expression (fold change between two groups >32.12, P≤0.0001). In conclusion, results of the present study indicate that methylation of the OPRK1 promoter contributes to the pathophysiology of drug addiction.

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The Association of Genetic Polymorphisms in the κ-Opioid Receptor 1 Gene With Body Weight, Alcohol Use, and Withdrawal Symptoms in Patients With Methadone Maintenance

Cited by 30 publications

References 33 publications

Clinical-genetic model predicts incident impulse control disorders in Parkinson's disease

Clinical-genetic model predicts incident impulse control disorders in Parkinson's disease

Alcohol Use Disorders in Opioid Maintenance Therapy: Prevalence, Clinical Correlates and Treatment

Hypermethylation of the κ1 opioid receptor promoter in Chinese heroin and methamphetamine addicts

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