Short Tandem Repeat Variation in the CNR1 Gene Associated With Analgesic Requirements of Opioids in Postoperative Pain Management.
Short Tandem Repeat Variation in the CNR1 Gene Associated With Analgesic Requirements of Opioids in Postoperative Pain Management.
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DOI：
10.3389/fgene.2022.815089
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发表时间：
2022
影响因子：
3.7
通讯作者：
Ikeda K
中科院分区：
文献类型：
--
作者：
Kasai S;Nishizawa D;Hasegawa J;Fukuda KI;Ichinohe T;Nagashima M;Hayashida M;Ikeda K
短串联重复序列（STR）和可变数目串联重复序列（VNTR）已分别在人类基因组中的大约70万和50万个位点处被鉴定，是高度多等位基因变异而不是单核苷酸多态性。超过几千个STR的重复数量与附近基因的表达相关，表明STR是人类性状中有影响力的遗传变异。镇痛剂通过其内在受体作用于中枢神经系统以产生镇痛作用。在本研究中，我们专注于CNR 1，GRIN 2A，PENK和PDYN基因中的STR和VNTR，并分析了术后疼痛管理中的两个外周疼痛感觉相关特征和七个疼痛相关特征。共有192名志愿者接受了外周痛觉测试，139名和252名患者接受了开放性腹部和正颌美容手术，分别被纳入本研究。四种STR或VNTR均与外周痛觉无关。CNR 1、GRIN 2A和PENK基因中的短串联重复序列与芬太尼使用频率、芬太尼剂量和正颌美容手术后3小时视觉模拟量表疼痛评分相关（斯皮尔曼秩相关系数分别为ρ = 0.199，p = 0.002，ρ = 0.174，p = 0.006和ρ = 0.135，p = 0.033），镇痛剂量，包括开腹手术后硬膜外镇痛药（ρ =-0.200，p = 0.018）和正颌美容手术后24 h视觉模拟量表疼痛评分（ρ = 0.143，p = 0.023）。通过霍尔姆多重检验校正，证实了CNR 1基因STR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。这些研究结果表明，在CNR 1基因的STR影响镇痛口面区域。
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 CNR1, GRIN2A, PENK, and PDYN 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 CNR1, GRIN2A, and PENK 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 ρ = 0.199, p = 0.002, ρ = 0.174, p = 0.006, and ρ = 0.135, p = 0.033, respectively), analgesic dose, including epidural analgesics after open abdominal surgery (ρ = −0.200, p = 0.018), and visual analog scale pain scores 24 h after orthognathic cosmetic surgery (ρ = 0.143, p = 0.023), respectively. The associations between STRs in the CNR1 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 CNR1 gene influence analgesia in the orofacial region.
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影响因子：
16.6
作者：
Bakhtiari M;Park J;Ding YC;Shleizer-Burko S;Neuhausen SL;Halldórsson BV;Stefánsson K;Gymrek M;Bafna V
通讯作者：
Bafna V
影响因子：
9.8
作者：
Brinkmann, B;Klintschar, M;Rolf, B
通讯作者：
Rolf, B
影响因子：
7.4
作者：
Bisgaard, T;Klarskov, B;Kehlet, H
通讯作者：
Kehlet, H
影响因子：
3.1
作者：
Candiotti, Keith;Yang, Zhe;Gitlin, Melvin
通讯作者：
Gitlin, Melvin
影响因子：
16.6
作者：
Jakubosky, David;D'Antonio, Matteo;Frazer, Kelly A.
通讯作者：
Frazer, Kelly A.