阿片类药物使用障碍 (OUD) 是一种受性别、遗传和环境因素影响的多方面疾病，这些因素可能与表观遗传变化有关。了解这些因素如何相互作用对于理解和解决这种疾病的发展和进展至关重要。我们的目的是阐明女性和男性之间不同的潜在表观遗传和遗传机制，这些机制与真实世界疼痛单位条件下的 OUD 相关。在 345 例长期接受阿片类药物治疗的慢性非癌性疼痛：OUD 病例中评估了镇痛反应与阿片类药物 mu 受体 (OPRM1) 基因（启动子区域中选择的 CpG 位点 1-5）的 DNA 甲基化水平之间的关联（n = 67 ）和对照（无 OUD，n = 278）。与对照组相比，病例显示年龄较小、就业状况和生活质量较低，但吗啡当量每日剂量和精神药物使用较高。 OUD 患者的 OPRM1 DNA 甲基化显着降低，这与疼痛缓解、抑郁和不同不良事件等临床结果相关。在针对男性研究的 5 个 CpG 位点中发现了与 OUD 诊断相关的显着差异，并且仅针对女性的 CpG 位点 3 发现了显着差异。这些发现支持了表观遗传学和性别作为生物变量的重要性，需要考虑有效的 OUD 理解和治疗开发。© 2024 作者。约翰·威利出版的《成瘾生物学》

Opioid use disorder (OUD) is a multifaceted condition influenced by sex, genetic and environmental factors that could be linked with epigenetic changes. Understanding how these factors interact is crucial to understand and address the development and progression of this disorder. Our aim was to elucidate different potential epigenetic and genetic mechanisms between women and men that correlate with OUD under real-world pain unit conditions. Associations between analgesic response and the DNA methylation level of the opioid mu receptor (OPRM1) gene (CpG sites 1-5 selected in the promoter region) were evaluated in 345 long opioid-treated chronic non cancer pain: cases with OUD (n = 67) and controls (without OUD, n = 278). Cases showed younger ages, low employment status and quality of life, but higher morphine equivalent daily dose and psychotropic use, compared to the controls. The patients with OUD showed a significant decrease in OPRM1 DNA methylation, which correlated with clinical outcomes like pain relief, depression and different adverse events. Significant differences were found at the five CpG sites studied for men, and exclusively in women for CpG site 3, in relation to OUD diagnosis. These findings support the importance of epigenetics and sex as biological variables to be considered toward efficient OUD understanding and therapy development.© 2024 The Author(s). Addiction Biology published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.