Neuroscience Graduate Program, McMaster University, Hamilton, ON, Canada.
Department of Psychiatry and Behavioural Neurosciences, St. Joseph's Healthcare Hamilton, 100 West 5th St., Hamilton, ON, L8N3K7, Canada.
Addict Sci Clin Pract. 2021 Nov 27;16(1):70. doi: 10.1186/s13722-021-00278-y.
Patients 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.
This systematic review aims to summarize genome-wide significant findings on MOUD outcomes and critically appraise the quality of the studies involved.
Databases 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.
Our 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. 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.
The limitations of this study include not being able to synthesize the data in a quantitative way and a conservative eligibility and data collection model.
The 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.
患有阿片类药物使用障碍（OUD）的患者对治疗阿片类药物使用障碍（MOUD）的药物反应存在个体间差异。遗传基础可能可以解释这种反应的变异性。然而，对于哪些遗传变异显著影响 MOUD 结局，尚未达成共识。
本系统评价旨在总结 MOUD 结局的全基因组显著发现，并批判性地评价所涉及研究的质量。
从创建到 2020 年 8 月 21 日，检索了数据库包括：MEDLINE、Web of Science、EMBASE、CINAHL 和 Pre-CINAHL、GWAS Catalog 和 GWAS Central。纳入的研究必须是评估 OUD 人群中 MOUD 的 GWAS。所有研究均进行了重复筛选。使用 Q-Genie 工具对纳入研究的质量进行评分和评估。由于方案中计划进行定量分析，因此无法进行分析，因此对研究进行了定性分析。
我们的搜索确定了 7292 项研究。符合入选标准的有 5 项研究。然而，只有 3 项研究报告的结果达到了我们设定的 p 值 ≤ 1.0 × 10 的显著性阈值。总共鉴定出 43 个遗传变异。对应于 CNIH3 的变异被报道与欧洲人的每日海洛因注射有关，OPRM1、TRIB2 和 ZNF146 与非洲裔美国人的美沙酮剂量有关，EYS 与欧洲人的美沙酮剂量有关，SPON1 和染色体 9 和 3 上的基因间区域与 S-美沙酮、R-美沙酮和 R-EDDP 的血浆浓度分别相关，在汉族中。
本研究的局限性包括无法以定量方式综合数据，以及采用保守的入选标准和数据收集模型。
本系统评价的结果将有助于突出具有显著遗传变异的基因，这些基因可以在未来的 OUD 药物遗传学研究中复制，以确定它们在患者特定的 MOUD 结局中的作用。系统评价注册号 CRD42020169121。
