Nishizawa Daisuke, Nagashima Makoto, Kasai Shinya, Hasegawa Junko, Nakayama Kyoko, Ebata Yuko, Fukuda Ken-Ichi, Ichinohe Tatsuya, Hayashida Masakazu, Ikeda Kazutaka
Addictive Substance Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan.
Department of Surgery, Toho University Sakura Medical Center, Sakura 143-8541, Japan.
Pharmaceutics. 2022 Mar 28;14(4):727. doi: 10.3390/pharmaceutics14040727.
Considerable individual differences are widely observed in the sensitivity to opioid analgesics. We focused on rs12496846, rs698705, and rs10052295 single-nucleotide polymorphisms (SNPs) in the C3orf20, SLC8A2, and CTNND2 gene regions that we previously identified as possibly associated with postoperative analgesia after orthognathic surgery. We investigated associations between these SNPs and postoperative analgesia in 112 patients who underwent major open abdominal surgery in hospitals and were treated with analgesics, including opioids, after surgery. Total genomic DNA was extracted from peripheral blood or oral mucosa samples for genotyping each SNP. Effects of these potent SNPs on gene expression in the brain were also investigated in samples that were provided by the Stanley Foundation Brain Bank. In the association studies, carriers of the G allele of the rs12496846 SNP in the C3orf20 gene region were significantly associated with greater 24 h postoperative analgesic requirements among the three SNPs that were investigated (p = 0.0015), which corroborated a previous study of orthognathic patients (p < 0.0001). In the gene expression analysis, carriers of the G allele of the rs12496846 SNP were significantly associated with lower mRNA expression of the C3orf20 gene (p < 0.0001). These results indicate that this SNP could serve as a marker that predicts analgesic requirements.
在对阿片类镇痛药的敏感性方面，人们广泛观察到了相当大的个体差异。我们聚焦于C3orf20、SLC8A2和CTNND2基因区域中的rs12496846、rs698705和rs10052295单核苷酸多态性（SNP），我们之前确定这些多态性可能与正颌外科手术后的术后镇痛有关。我们调查了这些SNP与112例在医院接受大型开放性腹部手术并在术后接受包括阿片类药物在内的镇痛药治疗的患者术后镇痛之间的关联。从外周血或口腔黏膜样本中提取总基因组DNA，用于对每个SNP进行基因分型。还在斯坦利基金会脑库提供的样本中研究了这些强效SNP对大脑基因表达的影响。在关联研究中，在研究的三个SNP中，C3orf20基因区域rs12496846 SNP的G等位基因携带者与术后24小时更高的镇痛需求显著相关（p = 0.0015），这证实了之前对正颌患者的研究结果（p < 0.0001）。在基因表达分析中，rs12496846 SNP的G等位基因携带者与C3orf20基因较低的mRNA表达显著相关（p < 0.0001）。这些结果表明，这个SNP可以作为预测镇痛需求的一个标志物。
