A single nucleotide polymorphism-based formula to predict the risk of propofol TCI concentration being over 4 µg mL−1 at the time of loss of consciousness

IF 2.9 3区医学 Q2 GENETICS & HEREDITY

Pharmacogenomics Journal Pub Date : 2022-01-22 DOI:10.1038/s41397-021-00263-3

Zhuoling Zheng, Faling Xue, Haini Wang, Yongqi He, Lingyi Zhang, Wudi Ma, Caibin Zhang, Yanping Guan, Fang Ye, Yongzi Wen, Xiaoyan Li, Min Huang, Wenqi Huang, Zhongxing Wang, Jiali Li

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引用次数: 2

Abstract

We aim to develop a formula based on single nucleotide polymorphisms (SNPs) to predict whether the propofol target-controlled infusion (TCI) concentration would be over 4 μg mL−1 at the time of loss of consciousness (LOC). We recruited 184 patients undergoing thyroid or breast surgeries with propofol anaesthesia. A total of 48 SNPs of CYP2B6, CYP2C9, UGT1A9, HNF4A, ABCB1, ABCC4, ABCG2, GABRA2, GABRA4, GABRB1, GABRB3, GABRG2, GABBR2, GAD1, SLC1A3, BDNF, and NRXN1, previously associated with propofol metabolic and pharmacology pathway, were genotyped. The formula was developed in the training cohort using the least absolute shrinkage and selection operator logistic regression model, and then validated in the testing cohort. The SNPs, GABBR2 rs1167768, GABBR2 rs1571927, NRXN1 rs601010, BDNF rs2049046, GABRA4 rs1512135, UGT1A9 rs11692021, GABBR2 rs2808536, HNF4A rs1884613, GABRB3 rs2017247, and CYP2B6 rs3181842 were selected to construct the SNP-based formula, which was used to calculate the risk score for over 4 μg mL−1 TCI concentration of propofol at the time of LOC. Patients in the high-risk group were more likely to require a propofol concentration higher than 4 μg mL−1 and presented a longer LOC latency. The SNP-based formula may significantly improve the safety and effectiveness of propofol-induced anaesthesia.

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基于单核苷酸多态性的公式预测意识丧失时丙泊酚 TCI 浓度超过 4 µg mL-1 的风险

我们旨在开发一种基于单核苷酸多态性（SNPs）的公式，用于预测意识丧失（LOC）时异丙酚靶控输注（TCI）浓度是否超过 4 μg mL-1。我们招募了 184 名接受甲状腺或乳腺手术并使用异丙酚麻醉的患者。我们对以前与异丙酚代谢和药理途径相关的 CYP2B6、CYP2C9、UGT1A9、HNF4A、ABCB1、ABCC4、ABCG2、GABRA2、GABRA4、GABRB1、GABRB3、GABRG2、GABBR2、GAD1、SLC1A3、BDNF 和 NRXN1 共 48 个 SNPs 进行了基因分型。利用最小绝对收缩和选择算子逻辑回归模型在训练队列中建立了公式，然后在测试队列中进行了验证。这些 SNPs 包括：GABBR2 rs1167768、GABBR2 rs1571927、NRXN1 rs601010、BDNF rs2049046、GABRA4 rs1512135、UGT1A9 rs11692021、GABBR2 rs2808536、HNF4A rs1884613、GABRB3 rs2017247、选择这些基因构建了基于 SNP 的公式，用于计算 LOC 时丙泊酚浓度超过 4 μg mL-1 TCI 的风险评分。高风险组患者更有可能需要使用浓度高于 4 μg mL-1 的异丙酚，并且 LOC 潜伏期更长。基于 SNP 的配方可大大提高异丙酚诱导麻醉的安全性和有效性。

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来源期刊

Pharmacogenomics Journal 医学-药学

CiteScore

7.20

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： The Pharmacogenomics Journal is a print and electronic journal, which is dedicated to the rapid publication of original research on pharmacogenomics and its clinical applications. Key areas of coverage include: Personalized medicine Effects of genetic variability on drug toxicity and efficacy Identification and functional characterization of polymorphisms relevant to drug action Pharmacodynamic and pharmacokinetic variations and drug efficacy Integration of new developments in the genome project and proteomics into clinical medicine, pharmacology, and therapeutics Clinical applications of genomic science Identification of novel genomic targets for drug development Potential benefits of pharmacogenomics.