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全子宫切除术后急性和慢性疼痛及吗啡用量的SCN9A基因变异分析

Analysis of SCN9A Gene Variants for Acute and Chronic Postoperative Pain and Morphine Consumption After Total Hysterectomy.

作者信息

Yeo Junjie, Sia Alex T, Sultana Rehana, Sng Ban Leong, Tan Ene-Choo

机构信息

Ministry of Health Holdings, Singapore.

Department of Women's Anaesthesia, KK Women's and Children's Hospital, Singapore.

出版信息

Pain Med. 2020 Nov 1;21(11):2642-2649. doi: 10.1093/pm/pnaa109.

Abstract

BACKGROUND

Single nucleotide polymorphisms (SNPs) of the voltage-gated sodium channel alpha subunit gene (SCN9A) have been associated with pain in various settings. The aim of this study was to investigate the association of the SNPs to evaluate the influence of common gene variants on chronic postoperative pain (CPSP) and other related pain variables in a cohort of patients who underwent a scheduled hysterectomy.

METHODS

DNA samples from a cohort of 1,075 patients who underwent a scheduled total hysterectomy in our hospital were genotyped for three common SCN9A SNPs using TaqMan assays. Multivariate logistic regression models were used to quantify the association between independent covariates such as pain threshold, pain endurance, pain scores, morphine use, and the presence of chronic pain.

RESULTS

Frequencies of the minor alleles were different between the different ethnic groups. There was a statistically significant association of rs16851799 with morphine consumption and self-reported postoperative pain for the 1,038 subjects genotyped, with the TT genotype reporting higher pain and using more morphine. For the subpopulation of 446 subjects with chronic pain data, there was a similar association with self-reported postoperative pain and tolerance of pressure pain. Univariate analysis also showed a statistically significant association of rs16851799 with CPSP, whereas multivariable analysis revealed a similar association of rs4387806 with this outcome. There were three haplotypes with different relative frequencies for the CPSP and non-CPSP groups.

CONCLUSIONS

Our results showed that SCN9A polymorphisms could play a role in acute pain perception and the susceptibility to chronic pain.

摘要

背景

电压门控钠通道α亚基基因(SCN9A)的单核苷酸多态性(SNP)已在多种情况下与疼痛相关。本研究的目的是调查SNP的关联性,以评估常见基因变异对接受择期子宫切除术患者队列中慢性术后疼痛(CPSP)及其他相关疼痛变量的影响。

方法

采用TaqMan分析法,对我院1075例接受择期全子宫切除术患者队列的DNA样本进行三种常见SCN9A SNP的基因分型。使用多变量逻辑回归模型量化独立协变量之间的关联,如疼痛阈值、疼痛耐受力、疼痛评分、吗啡使用情况以及慢性疼痛的存在。

结果

不同种族群体中次要等位基因的频率不同。对于1038例进行基因分型的受试者,rs16851799与吗啡消耗量及自我报告的术后疼痛存在统计学显著关联,TT基因型报告的疼痛程度更高且使用的吗啡更多。对于有慢性疼痛数据的446例受试者亚组,rs16851799与自我报告的术后疼痛及压力疼痛耐受性也存在类似关联。单因素分析还显示rs16851799与CPSP存在统计学显著关联,而多变量分析显示rs4387806与该结果存在类似关联。CPSP组和非CPSP组有三种相对频率不同的单倍型。

结论

我们的结果表明,SCN9A多态性可能在急性疼痛感知和慢性疼痛易感性中起作用。

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