Addictive Substance Project, Tokyo Metropolitan Institute of Medical Science, Setagaya-ku, Tokyo 156-8506, Japan.
Department of Dental Anesthesiology, Tokyo Dental College, Chiyoda-ku, Tokyo 101-0061, Japan.
Int J Mol Sci. 2024 Aug 14;25(16):8845. doi: 10.3390/ijms25168845.
Opioids are almost mandatorily used for analgesia for cancer pain and postoperative pain. Opioid analgesics commonly induce nausea as a side effect. However, the genetic factors involved are still mostly unknown. To clarify the genetic background of individual differences in the occurrence of nausea during opioid administration, the incidence of nausea was investigated in 331 patients (Higashi-Sapporo Hospital [HS] group) who received morphine chronically for cancer pain treatment and in 2021 patients (Cancer Institute Hospital [CIH] group) who underwent elective surgery under general anesthesia. We conducted a genome-wide association study of nausea in HS samples. Among the top 20 candidate single-nucleotide polymorphisms (SNPs), we focused on the rs7296262 SNP, which has been reportedly associated with psychiatric disorders. The rs7296262 SNP was significantly associated with nausea in both the HS and CIH groups (TT+TC vs. CC; HS group, = 0.0001; CIH group, = 0.0064). The distribution of nausea-prone genotypes for the rs7296262 SNP was reversed between HS and CIH groups. These results suggest that the rs7296262 SNP is significantly associated with nausea during opioid use, and the effect of the SNP genotype on nausea is reversed between chronic and acute phases of opioid use.
阿片类药物几乎是癌症疼痛和术后疼痛镇痛的强制性药物。阿片类镇痛药通常会引起恶心等副作用。然而,涉及的遗传因素在很大程度上仍然未知。为了阐明阿片类药物给药期间恶心发生的个体差异的遗传背景,我们调查了 331 名接受吗啡慢性癌症疼痛治疗的患者(东札幌医院[HS]组)和 2021 名接受全身麻醉下择期手术的患者(癌症研究所医院[CIH]组)在接受阿片类药物时发生恶心的发生率。我们对 HS 样本进行了全基因组关联研究。在排名前 20 的候选单核苷酸多态性(SNP)中,我们重点关注了 rs7296262 SNP,该 SNP 已被报道与精神疾病有关。rs7296262 SNP 与 HS 和 CIH 组的恶心均显著相关(TT+TC 与 CC;HS 组, = 0.0001;CIH 组, = 0.0064)。rs7296262 SNP 的恶心易感基因型在 HS 和 CIH 组之间的分布相反。这些结果表明,rs7296262 SNP 与阿片类药物使用期间的恶心显著相关,并且 SNP 基因型对恶心的影响在阿片类药物的慢性和急性阶段之间相反。