Department of Clinical Pharmacy Research and Education (M.T., K.N., K.I.), Osaka University Graduate School of Pharmaceutical Sciences, Suita, Osaka, Japan; Department of Pharmacy (M.T., K.N., Y.O.), Ashiya Municipal Hospital, Ashiya, Hyogo, Japan.
Department of Clinical Pharmacy Research and Education (M.T., K.N., K.I.), Osaka University Graduate School of Pharmaceutical Sciences, Suita, Osaka, Japan; Department of Pharmacy (M.T., K.N., Y.O.), Ashiya Municipal Hospital, Ashiya, Hyogo, Japan.
J Pain Symptom Manage. 2024 Jan;67(1):39-49.e5. doi: 10.1016/j.jpainsymman.2023.09.017. Epub 2023 Sep 26.
μ-opioid receptor gene (OPRM1) A118G polymorphism (rs1799971) causes loss of N-glycosylation sites at the extracellular domain of μ-opioid receptors. G-allele carriers show a limited response to morphine; however, studies investigating the impact of A118G polymorphism on the efficacy of opioids other than morphine are limited.
To compare the impact of A118G polymorphism on the efficacy of various opioids.
This prospective cohort study enrolled 222 in-patients administered one of the following opioid therapies for cancer pain as part of an opioid introduction or rotation strategy: tapentadol extended-release tablets, methadone tablets, hydromorphone controlled-release tablets, oxycodone controlled-release tablets, or transdermal fentanyl patches. The impact of A118G polymorphism on the difference in the Brief Pain Inventory-Short Form score on days three, seven, and 14 from baseline was compared among the groups.
Overall, 81, 74, and 67 patients had the AA, AG, and GG genotypes, respectively, with an OPRM1 A118G G-allele variant frequency of 0.47. The reduction in the Brief Pain Inventory-Short Form score after opioid therapy initiation did not differ significantly among the patients with the three A118G genotypes treated with tapentadol (p = 0.84) or methadone (p = 0.97), whereas it was significantly smaller in G-allele carriers than that in AA homozygous patients treated with hydromorphone (p < 0.001), oxycodone (p = 0.031), or fentanyl (p < 0.001).
Tapentadol and methadone may be more suitable than hydromorphone, oxycodone, and fentanyl for G-allele carriers due to their dual mechanism of action and low susceptibility to OPRM1 A118G polymorphism.
μ-阿片受体基因（OPRM1）A118G 多态性（rs1799971）导致μ-阿片受体细胞外结构域失去 N-糖基化位点。G 等位基因携带者对吗啡的反应有限；然而，研究调查 A118G 多态性对除吗啡以外的阿片类药物疗效的影响的研究有限。
比较 A118G 多态性对各种阿片类药物疗效的影响。
这项前瞻性队列研究纳入了 222 名接受以下阿片类药物治疗的住院患者，这些患者接受了阿片类药物治疗以缓解癌症疼痛，包括作为阿片类药物引入或轮换策略的一部分：盐酸他喷他多缓释片、盐酸美沙酮片、氢吗啡酮控释片、盐酸羟考酮控释片或芬太尼透皮贴剂。比较各组患者从基线开始第 3、7 和 14 天的简明疼痛量表（Brief Pain Inventory-Short Form，BPI-SF）评分差异与 A118G 多态性的关系。
总体而言，81、74 和 67 例患者分别具有 AA、AG 和 GG 基因型，OPRM1 A118G G 等位基因变异频率为 0.47。接受他喷他多或美沙酮治疗的三组 A118G 基因型患者的 BPI-SF 评分在阿片类药物治疗开始后的下降程度无显著差异（p=0.84 或 p=0.97），而与 AA 纯合子患者相比，G 等位基因携带者的下降程度明显较小，接受氢吗啡酮（p<0.001）、羟考酮（p=0.031）或芬太尼（p<0.001）治疗的患者的下降程度较小。
由于双重作用机制和对 OPRM1 A118G 多态性的低敏感性，他喷他多和美沙酮可能比氢吗啡酮、羟考酮和芬太尼更适合 G 等位基因携带者。
