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
{"title":"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","authors":"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","doi":"10.1038/s41397-021-00263-3","DOIUrl":null,"url":null,"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.","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":"22 2","pages":"109-116"},"PeriodicalIF":2.9000,"publicationDate":"2022-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"2","resultStr":"{\"title\":\"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\",\"authors\":\"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\",\"doi\":\"10.1038/s41397-021-00263-3\",\"DOIUrl\":null,\"url\":null,\"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.\",\"PeriodicalId\":54624,\"journal\":{\"name\":\"Pharmacogenomics Journal\",\"volume\":\"22 2\",\"pages\":\"109-116\"},\"PeriodicalIF\":2.9000,\"publicationDate\":\"2022-01-22\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"2\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pharmacogenomics Journal\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.nature.com/articles/s41397-021-00263-3\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"GENETICS & HEREDITY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pharmacogenomics Journal","FirstCategoryId":"3","ListUrlMain":"https://www.nature.com/articles/s41397-021-00263-3","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
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
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.
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.