Abstract
BackgroundPatients with opioid use disorder (OUD) display an interindividual variability in their response to medications for opioid use disorder (MOUD). A genetic basis may explain the variability in this response. However, no consensus has been reached regarding which genetic variants significantly contribute to MOUD outcomes.ObjectivesThis systematic review aims to summarize genome-wide significant findings on MOUD outcomes and critically appraise the quality of the studies involved.MethodsDatabases searched from inception until August 21st, 2020 include: MEDLINE, Web of Science, EMBASE, CINAHL and Pre-CINAHL, GWAS Catalog and GWAS Central. The included studies had to be GWASs that assessed MOUD in an OUD population. All studies were screened in duplicate. The quality of the included studies was scored and assessed using the Q-Genie tool. Quantitative analysis, as planned in the protocol, was not feasible, so the studies were analyzed qualitatively.ResultsOur search identified 7292 studies. Five studies meeting the eligibility criteria were included. However, only three studies reported results that met our significance threshold of p ≤ 1.0 × 10–7. In total, 43 genetic variants were identified. Variants corresponding to CNIH3 were reported to be associated with daily heroin injection in Europeans, OPRM1, TRIB2, and ZNF146 with methadone dose in African Americans, EYS with methadone dose in Europeans, and SPON1 and intergenic regions in chromosomes 9 and 3 with plasma concentrations of S-methadone, R-methadone, and R-EDDP, respectively, in Han Chinese.LimitationsThe limitations of this study include not being able to synthesize the data in a quantitative way and a conservative eligibility and data collection model.ConclusionThe results from this systematic review will aid in highlighting significant genetic variants that can be replicated in future OUD pharmacogenetics research to ascertain their role in patient-specific MOUD outcomes.Systematic review registration number CRD42020169121.
Highlights
Patients with opioid use disorder (OUD) display an interindividual variability in their response to medications for opioid use disorder (MOUD)
Following title and abstract screening, 38 studies were deemed relevant for full-text screening, and 5771 studies were excluded due to not being Genome-wide association study (GWAS), not assessing an OUD population, and/or not assessing a MOUD
Ancestries of the participants included in these GWASs were European, African American, and/or Han Chinese, with Europeans constituting the largest sample
Summary
Patients with opioid use disorder (OUD) display an interindividual variability in their response to medications for opioid use disorder (MOUD). Rationale Opioid use has been on the rise over the past decade, causing the United States and Canada, amongst other. In a 2019 report, the United Nations estimated about 53 million past-year users of opioids for 2017 worldwide [3]. 110,000 deaths were attributed to opioid use [3]. Treatments for opioid use disorder (OUD) have become more available and accessible under the term medication-assisted treatments or medications for opioid use disorder (MOUD). MOUD include the controlled administration of an opioid agonist or antagonist along with behavioural therapy or counselling with the objective of full recovery from opioid use [4]. Pharmacological agents of MOUD include the commonly used methadone, buprenorphine, buprenorphine/naloxone combination, naltrexone, heroin-assisted treatment, and sustained release morphine
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