OPRM1 rs1799971 Polymorphism and Opioid Dependence: Evidence from a Meta-Analysis

Abstract

The OPRM1 gene encodes the µ-opioid receptor, which is the primary site of action of most opioids. Several studies and three meta-analyses have examined a possible link between the exonic OPRM1 A118G (rs1799971) polymorphism and opioid dependence; however, results have been inconclusive. Therefore, a systematic review and meta-analysis have been carried out to examine whether this polymorphism is associated with opioid dependence. Thirteen studies (n = 9385), comprising 4601 opioid dependents and 4784 controls, which evaluated association of the OPRM1 rs1799971 polymorphism with susceptibility to opioids, were included in this study. Our meta-analysis showed significant association between this polymorphism and susceptibility to opioid dependence in overall studies under a codominant model, as well as susceptibility to opioid dependence or heroin dependence in Asians under an autosomal dominant model. The nonsynonymous OPRM1 rs1799971 might be a risk factor for addiction to opioids or heroin in an Asian population.

On the Role of Genetic Testing for Personalized Drug Overdose Management

“…Consistent with the results of our study, multiple investigations have reported an association of the 118G allele with opioid abuse [4][5][6]. However, the mu opioid receptor is involved in multiple physiological functions, thus the 118G allele could be beneficial for some processes, but adverse for others.…”

Battling the Opiate Crisis: Translating the Latest Advances in Addiction Biology into Novel Treatment Strategies

“…The µ opiate receptor is the site where opiates produce their characteristic pharmacological effects such as analgesia, sedation, slightly reduced blood pressure, itching, nausea, euphoria, respiratory depression, miosis, and decreased bowel motility leading to constipation [35]. The A118G polymorphism in the OPRM1 gene results in a decrease in expression of μ opiate receptors and decreased functionality of the expressed receptors, which may decrease the analgesic response to opiates.…”

“…Patients with this variant have shown a lower pain threshold and a higher drug consumption to achieve effective analgesia. Because of its functional significance, this variant (rs1799971, A118G, Asn40Asp) in OPRM1 has been extensively studied in addiction [35,36]. A collaborative meta-analyses of 25 data-sets with over 28,000 European-ancestry subjects investigated this OPRM1 mutation for non-specific risk for ''general'' substance dependence [36].…”

“…Paradoxically, this same mutation results in an apparent gain of function with respect to response to endogenous opioids, like β-endorphins. Individuals who carry at least 1 G allele have significantly better outcomes with naltrexone therapy for alcoholism and drug abuse [35][36][37][38][39].…”

Stabilization of remission in patients with opioid dependence with naltrexone implant: a pharmacogenetic approach

“…Это не подтверждает данных [24] о том, что локус A118G SNP гена мю-опиоидного рецептора (OPRM1) связан с героиновой наркоманией, но хо-рошо согласуется с другими результатами по этни-чески близкой популяции [25], не выявившими вли-яния этого локуса у больных опийной наркоманией, в отличие от многочисленных позитивных находок для алкогольной зависимости. Однако, возможно, что в некоторых популяциях, например в азиатских, связь имеется [26], что еще раз подчеркивает необ-ходимость строгого контроля этнической однород-ности изучаемых когорт больных.…”