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与术后疼痛管理中阿片类药物镇痛需求相关基因的短串联重复序列变异

Short Tandem Repeat Variation in the Gene Associated With Analgesic Requirements of Opioids in Postoperative Pain Management.

作者信息

Kasai Shinya, Nishizawa Daisuke, Hasegawa Junko, Fukuda Ken-Ichi, Ichinohe Tatsuya, Nagashima Makoto, Hayashida Masakazu, Ikeda Kazutaka

机构信息

Addictive Substance Project, Department of Psychiatry and Behavioral Sciences, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.

Department of Oral Health Science, Tokyo Dental College, Tokyo, Japan.

出版信息

Front Genet. 2022 Mar 3;13:815089. doi: 10.3389/fgene.2022.815089. eCollection 2022.

Abstract

Short tandem repeats (STRs) and variable number of tandem repeats (VNTRs) that have been identified at approximately 0.7 and 0.5 million loci in the human genome, respectively, are highly multi-allelic variations rather than single-nucleotide polymorphisms. The number of repeats of more than a few thousand STRs was associated with the expression of nearby genes, indicating that STRs are influential genetic variations in human traits. Analgesics act on the central nervous system via their intrinsic receptors to produce analgesic effects. In the present study, we focused on STRs and VNTRs in the , , , and genes and analyzed two peripheral pain sensation-related traits and seven analgesia-related traits in postoperative pain management. A total of 192 volunteers who underwent the peripheral pain sensation tests and 139 and 252 patients who underwent open abdominal and orthognathic cosmetic surgeries, respectively, were included in the study. None of the four STRs or VNTRs were associated with peripheral pain sensation. Short tandem repeats in the , , and genes were associated with the frequency of fentanyl use, fentanyl dose, and visual analog scale pain scores 3 h after orthognathic cosmetic surgery (Spearman's rank correlation coefficient = 0.199, = 0.002, = 0.174, = 0.006, and = 0.135, = 0.033, respectively), analgesic dose, including epidural analgesics after open abdominal surgery ( = -0.200, = 0.018), and visual analog scale pain scores 24 h after orthognathic cosmetic surgery ( = 0.143, = 0.023), respectively. The associations between STRs in the gene and the frequency of fentanyl use and fentanyl dose after orthognathic cosmetic surgery were confirmed by Holm's multiple-testing correction. These findings indicate that STRs in the gene influence analgesia in the orofacial region.

摘要

短串联重复序列(STRs)和可变数目串联重复序列(VNTRs)分别在人类基因组中约70万个和50万个位点被鉴定出来,它们是高度多等位基因变异,而非单核苷酸多态性。数千个以上STRs的重复次数与附近基因的表达相关,这表明STRs是影响人类性状的重要遗传变异。镇痛药通过其内在受体作用于中枢神经系统以产生镇痛效果。在本研究中,我们聚焦于 、 、 和 基因中的STRs和VNTRs,并在术后疼痛管理中分析了两种外周痛觉相关性状和七种镇痛相关性状。共有192名接受外周痛觉测试的志愿者以及分别接受腹部开放性手术和正颌美容手术的139名和252名患者纳入本研究。四个STRs或VNTRs均与外周痛觉无关。 、 和 基因中的短串联重复序列分别与正颌美容手术后3小时芬太尼使用频率、芬太尼剂量和视觉模拟评分疼痛分数(斯皮尔曼等级相关系数分别为 = 0.199, = 0.002, = 0.174, = 0.006,以及 = 0.135, = 0.033)、腹部开放性手术后包括硬膜外镇痛药在内的镇痛剂量( = -0.20, = 0.018)以及正颌美容手术后24小时视觉模拟评分疼痛分数( = 0.143, = 0.023)相关。通过霍尔姆多重检验校正证实了 基因中的STRs与正颌美容手术后芬太尼使用频率和芬太尼剂量之间的关联。这些发现表明 基因中的STRs影响口腔面部区域的镇痛作用。

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