Associations of Synaptosome-associated Protein 25 Gene Polymorphism, Autonomic Nervous System Activity, and Recovery of Consciousness from Propofol Anesthesia.
Gespeichert in:
| Titel: | Associations of Synaptosome-associated Protein 25 Gene Polymorphism, Autonomic Nervous System Activity, and Recovery of Consciousness from Propofol Anesthesia. |
|---|---|
| Autoren: | Ma G; Department of Anesthesiology, Lianyungang Clinical College of Xuzhou Medical University, Lianyungang, China., Wang Y; Department of Anesthesiology, Lianyungang Clinical College of Xuzhou Medical University, Lianyungang, China., Guan J; Department of Anesthesiology, Lianyungang Clinical College of Xuzhou Medical University, Lianyungang, China., Li C; Department of Anesthesiology, Lianyungang Clinical College of Xuzhou Medical University, Lianyungang, China., Ma T; School of Pharmacy, Nanjing Medical University, Nanjing, China., Gao X; Department of Central Laboratory, Second People's Hospital of Lianyungang, Lianyungang, China., Zhang J; Department of Anesthesiology, Lianyungang Clinical College of Xuzhou Medical University, Lianyungang, China. |
| Quelle: | Anesthesiology [Anesthesiology] 2025 Oct 01; Vol. 143 (4), pp. 894-905. Date of Electronic Publication: 2025 Jun 19. |
| Publikationsart: | Journal Article |
| Sprache: | English |
| Info zur Zeitschrift: | Publisher: Lippincott Williams & Wilkins Country of Publication: United States NLM ID: 1300217 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1528-1175 (Electronic) Linking ISSN: 00033022 NLM ISO Abbreviation: Anesthesiology Subsets: MEDLINE |
| Imprint Name(s): | Publication: Philadelphia Pa : Lippincott Williams & Wilkins Original Publication: Philadelphia : American Society of Anesthesiologists |
| MeSH-Schlagworte: | Propofol*/pharmacology , Synaptosomal-Associated Protein 25*/genetics , Polymorphism, Single Nucleotide*/genetics , Anesthetics, Intravenous*/pharmacology , Autonomic Nervous System*/drug effects , Autonomic Nervous System*/physiology , Consciousness*/drug effects , Anesthesia Recovery Period*, Humans ; Male ; Female ; Middle Aged ; Adult |
| Abstract: | Background: The release of synaptic neurotransmitters and function of presynaptic proteins are essential for maintaining nervous system excitation. General anesthesia is a reversible state characterized by the loss of consciousness and reduced responsiveness. This study hypothesized that polymorphisms in one or more genes encoding the three presynaptic proteins composing the soluble N-ethylmaleimide-sensitive fusion attachment protein receptor (SNARE) complex affect consciousness and autonomic nerve function during propofol anesthesia. Method: One hundred thirty preoperative patients volunteered to undergo a simulated anesthesia procedure. The participants were genotyped for candidate single-nucleotide polymorphisms using the Sanger method. Changes in verbal commands, eyelash reflexes, and the ability to hold a weighted object during anesthesia induction and recovery were recorded. Further, other anesthesia endpoints such as effector compartment concentrations (Ce), Bispectral Index (BCP-100; Beijing slgo Medical Technology Co., Ltd., China), heart rate variability, and peripheral perfusion index were explored based on the polymorphic site of significant differences in consciousness. Results: The median and interquartile range results show that the recovery time of verbal commands of the synaptosome-associated protein 25 (SNAP-25) rs6039822 G/G genotype (G/G vs . A/A, 319 [259 to 378] vs . 379 [318 to 466] s; P = 0.048) were shorter. Logistic regression analysis showed that SNAP-25 rs6039822 and sex were independent factors influencing the recovery of verbal commands (chi-square = 11.916; P = 0.008). Other consciousness indices, Ce, heart rate variability, and peripheral perfusion index, support the resistance of the SNAP-25 rs6039822 variant to anesthetic during recovery. Conclusions: Genetic variation in SNAP-25 gene is associated with the recovery of consciousness and autonomic nervous system activity during propofol anesthesia. This finding supports that the presynaptic proteins may be related to the mechanism of action of propofol. (Copyright © 2025 The Author(s). Published by Wolters Kluwer Health, Inc., on behalf of the American Society of Anesthesiologists.) |
| References: | Schupp M, Malsam J, Ruiter M, et al.: Interactions between SNAP-25 and synaptotagmin-1 are involved in vesicle priming, clamping spontaneous and stimulating evoked neurotransmission. J Neurosci 2016; 36:11865–80. doi:10.1523/JNEUROSCI.1011-16.2016. (PMID: 10.1523/JNEUROSCI.1011-16.2016) Zhang Y, Hughson FM: Chaperoning SNARE folding and assembly. Annu Rev Biochem 2021; 90:581–603. doi:10.1146/annurev-biochem-081820-103615. (PMID: 10.1146/annurev-biochem-081820-103615) Jahn R, Cafiso DC, Tamm LK: Mechanisms of SNARE proteins in membrane fusion. Nat Rev Mol Cell Biol 2024; 25:101–18. doi:10.1038/s41580-023-00668-x. (PMID: 10.1038/s41580-023-00668-x) van Swinderen B, Saifee O, Shebester L, Roberson R, Nonet ML, Crowder CM: A neomorphic syntaxin mutation blocks volatile-anesthetic action in Caenorhabditis elegans. Proc Natl Acad Sci U S A 1999; 96:2479–84. doi:10.1073/pnas.96.5.2479. (PMID: 10.1073/pnas.96.5.2479) Karunanithi S, Cylinder D, Ertekin D, et al.: Proportional downscaling of glutamatergic release sites by the general anesthetic propofol at Drosophila motor nerve terminals. eNeuro 2020; 7:ENEURO.0422–19.2020. doi:10.1523/ENEURO.0422-19.2020. (PMID: 10.1523/ENEURO.0422-19.2020) Zalucki OH, Menon H, Kottler B, et al.: Syntaxin1A-mediated resistance and hypersensitivity to isoflurane in Drosophila melanogaster. A nesthesiology 2015; 122:1060–74. doi:10.1097/ALN.0000000000000629. (PMID: 10.1097/ALN.0000000000000629) Troup M, Zalucki OH, Kottler BD, Karunanithi S, Anggono V, van Swinderen B: Syntaxin1A neomorphic mutations promote rapid recovery from isoflurane anesthesia in Drosophila melanogaster. A nesthesiology 2019; 131:555–68. doi:10.1097/ALN.0000000000002850. (PMID: 10.1097/ALN.0000000000002850) Herring BE, McMillan K, Pike CM, Marks J, Fox AP, Xie Z: Etomidate and propofol inhibit the neurotransmitter release machinery at different sites. J Physiol 2011; 589:1103–15. doi:10.1113/jphysiol.2010.200964. (PMID: 10.1113/jphysiol.2010.200964) Bademosi AT, Steeves J, Karunanithi S, et al.: Trapping of syntaxin1a in presynaptic nanoclusters by a clinically relevant general anesthetic. Cell Rep 2018; 22:427–40. doi:10.1016/j.celrep.2017.12.054. (PMID: 10.1016/j.celrep.2017.12.054) Brown EN, Lydic R, Schiff ND: General anesthesia, sleep, and coma. N Engl J Med 2010; 363:2638–50. doi:10.1056/NEJMra0808281. (PMID: 10.1056/NEJMra0808281) Mashour GA: Sleep, anesthesia, and consciousness. Sleep 2011; 34:247–8. doi:10.1093/sleep/34.3.247. (PMID: 10.1093/sleep/34.3.247) Bahador N, Kortelainen J: A robust bimodal index reflecting relative dynamics of EEG and HRV with application in monitoring depth of anesthesia. IEEE Trans Neural Syst Rehabil Eng 2021; 29:2503–10. doi:10.1109/TNSRE.2021.3128620. (PMID: 10.1109/TNSRE.2021.3128620) Subramanian S, Barbieri R, Purdon PL, Brown EN: Detecting loss and regain of consciousness during propofol anesthesia using multimodal indices of autonomic state. Annu Int Conf IEEE Eng Med Biol Soc 2020; 2020:824–7. doi:10.1109/EMBC44109.2020.9175366. (PMID: 10.1109/EMBC44109.2020.9175366) Tarvainen MP, Georgiadis S, Laitio T, et al.: Heart rate variability dynamics during low-dose propofol and dexmedetomidine anesthesia. Ann Biomed Eng 2012; 40:1802–13. doi:10.1007/s10439-012-0544-1. (PMID: 10.1007/s10439-012-0544-1) Kanaya N, Hirata N, Kurosawa S, Nakayama M, Namiki A: Differential effects of propofol and sevoflurane on heart rate variability. A nesthesiology 2003; 98:34–40. doi:10.1097/00000542-200301000-00009. (PMID: 10.1097/00000542-200301000-00009) Coutrot M, Dudoignon E, Joachim J, Gayat E, Vallée F, Dépret F: Perfusion index: Physical principles, physiological meanings and clinical implications in anaesthesia and critical care. Anaesth Crit Care Pain Med 2021; 40:100964. doi:10.1016/j.accpm.2021.100964. (PMID: 10.1016/j.accpm.2021.100964) Krishnamohan A, Siriwardana V, Skowno JJ: Using a pulse oximeter to determine clinical depth of anesthesia-investigation of the utility of the perfusion index. Paediatr Anaesth 2016; 26:1106–11. doi:10.1111/pan.13000. (PMID: 10.1111/pan.13000) Liu P-P, Wu C, Wu J-Z, et al.: The prediction probabilities for emergence from sevoflurane anesthesia in children: A comparison of the perfusion index and the Bispectral Index. Paediatr Anaesth 2018; 28:281–6. doi:10.1111/pan.13324. (PMID: 10.1111/pan.13324) Marteau TM, Bekker H: The development of a six-item short-form of the state scale of the Spielberger State-Trait Anxiety Inventory (STAI). Br J Clin Psychol 1992; 31:301–6. doi:10.1111/j.2044-8260.1992.tb00997.x. (PMID: 10.1111/j.2044-8260.1992.tb00997.x) Puri GD, Mathew PJ, Biswas I, et al.: A multicenter evaluation of a closed-loop anesthesia delivery system: A randomized controlled trial. Anesth Analg 2016; 122:106–14. doi:10.1213/ANE.0000000000000769. (PMID: 10.1213/ANE.0000000000000769) Gao Q, Liu L, Chen Y, et al.: Synaptosome-related (SNARE) genes and their interactions contribute to the susceptibility and working memory of attention-deficit/hyperactivity disorder in males. Prog Neuropsychopharmacol Biol Psychiatry 2015; 57:132–9. doi:10.1016/j.pnpbp.2014.11.001. (PMID: 10.1016/j.pnpbp.2014.11.001) Ye J, Coulouris G, Zaretskaya I, Cutcutache I, Rozen S, Madden TL: Primer-BLAST: A tool to design target-specific primers for polymerase chain reaction. BMC Bioinf 2012; 13:134. doi:10.1186/1471-2105-13-134. (PMID: 10.1186/1471-2105-13-134) van Swinderen B, Kottler B: Explaining general anesthesia: A two-step hypothesis linking sleep circuits and the synaptic release machinery. BioEssays 2014; 36:372–81. doi:10.1002/bies.201300154. (PMID: 10.1002/bies.201300154) Rosow C, Manberg PJ: Bispectral Index monitoring. Anesthesiol Clin North Am 2001; 19:947–66 xi. doi:10.1016/s0889-8537(01)80018-3. (PMID: 10.1016/s0889-8537(01)80018-3) Lan J-Y, Shieh J-S, Yeh J-R, Fan S-Z: Fractal properties of heart rate dynamics: A new biomarker for anesthesia-biphasic changes in general anesthesia and decrease in spinal anesthesia. Sensors (Basel) 2022; 22:9258. doi:10.3390/s22239258. (PMID: 10.3390/s22239258) Nagele P, Mendel JB, Placzek WJ, Scott BA, D’Avignon DA, Crowder CM: Volatile anesthetics bind rat synaptic snare proteins. A nesthesiology 2005; 103:768–78. doi:10.1097/00000542-200510000-00015. (PMID: 10.1097/00000542-200510000-00015) Yang X, Tu W, Gao X, Zhang Q, Guan J, Zhang J: Functional regulation of syntaxin-1: An underlying mechanism mediating exocytosis in neuroendocrine cells. Front Endocrinol 2023; 14:1096365. doi:10.3389/fendo.2023.1096365. (PMID: 10.3389/fendo.2023.1096365) Irfan M, Gopaul KR, Miry O, Hökfelt T, Stanton PK, Bark C: SNAP-25 isoforms differentially regulate synaptic transmission and long-term synaptic plasticity at central synapses. Sci Rep 2019; 9: 6403. doi:10.1038/s41598-019-42833-3. (PMID: 10.1038/s41598-019-42833-3) Vatta M: Intronic variants and splicing errors in cardiovascular diseases. Heart Rhythm 2009; 6:219–20. doi:10.1016/j.hrthm.2008.12.006. (PMID: 10.1016/j.hrthm.2008.12.006) Lin C-L, Taggart AJ, Fairbrother WG: RNA structure in splicing: An evolutionary perspective. RNA Biol 2016; 13:766–71. doi:10.1080/15476286.2016.1208893. (PMID: 10.1080/15476286.2016.1208893) Voorter CEM, Gerritsen KEH, Groeneweg M, Wieten L, Tilanus MGJ: The role of gene polymorphism in HLA class I splicing. Int J Immunogenet 2016; 43:65–78. doi:10.1111/iji.12256. (PMID: 10.1111/iji.12256) Hao X, Zhu B, Yang P, et al.: SNAP25 mutation disrupts metabolic homeostasis, steroid hormone production and central neurobehavior. Biochim Biophys Acta Mol Basis Dis 2022; 1868:166304. doi:10.1016/j.bbadis.2021.166304. (PMID: 10.1016/j.bbadis.2021.166304) Liu Y-S, Dai X, Wu W, et al.: The association of SNAP25 gene polymorphisms in attention deficit/hyperactivity disorder: A systematic review and meta-analysis. Mol Neurobiol 2017; 54:2189–200. doi:10.1007/s12035-016-9810-9. (PMID: 10.1007/s12035-016-9810-9) Thompson PM, Sower AC, Perrone-Bizzozero NI: Altered levels of the synaptosomal associated protein SNAP-25 in schizophrenia. Biol Psychiatry 1998; 43:239–43. doi:10.1016/S0006-3223(97)00204-7. (PMID: 10.1016/S0006-3223(97)00204-7) Wang Q, Wang Y, Ji W, et al.: SNAP25 is associated with schizophrenia and major depressive disorder in the Han Chinese population. J Clin Psychiatry 2015; 76:e76–82. doi:10.4088/JCP.13m08962. (PMID: 10.4088/JCP.13m08962) |
| Substance Nomenclature: | YI7VU623SF (Propofol) 0 (Synaptosomal-Associated Protein 25) 0 (Anesthetics, Intravenous) 0 (SNAP25 protein, human) |
| Entry Date(s): | Date Created: 20250619 Date Completed: 20250909 Latest Revision: 20250911 |
| Update Code: | 20250912 |
| PubMed Central ID: | PMC12416901 |
| DOI: | 10.1097/ALN.0000000000005627 |
| PMID: | 40537066 |
| Datenbank: | MEDLINE |
| Abstract: | Background: The release of synaptic neurotransmitters and function of presynaptic proteins are essential for maintaining nervous system excitation. General anesthesia is a reversible state characterized by the loss of consciousness and reduced responsiveness. This study hypothesized that polymorphisms in one or more genes encoding the three presynaptic proteins composing the soluble N-ethylmaleimide-sensitive fusion attachment protein receptor (SNARE) complex affect consciousness and autonomic nerve function during propofol anesthesia.<br />Method: One hundred thirty preoperative patients volunteered to undergo a simulated anesthesia procedure. The participants were genotyped for candidate single-nucleotide polymorphisms using the Sanger method. Changes in verbal commands, eyelash reflexes, and the ability to hold a weighted object during anesthesia induction and recovery were recorded. Further, other anesthesia endpoints such as effector compartment concentrations (Ce), Bispectral Index (BCP-100; Beijing slgo Medical Technology Co., Ltd., China), heart rate variability, and peripheral perfusion index were explored based on the polymorphic site of significant differences in consciousness.<br />Results: The median and interquartile range results show that the recovery time of verbal commands of the synaptosome-associated protein 25 (SNAP-25) rs6039822 G/G genotype (G/G vs . A/A, 319 [259 to 378] vs . 379 [318 to 466] s; P = 0.048) were shorter. Logistic regression analysis showed that SNAP-25 rs6039822 and sex were independent factors influencing the recovery of verbal commands (chi-square = 11.916; P = 0.008). Other consciousness indices, Ce, heart rate variability, and peripheral perfusion index, support the resistance of the SNAP-25 rs6039822 variant to anesthetic during recovery.<br />Conclusions: Genetic variation in SNAP-25 gene is associated with the recovery of consciousness and autonomic nervous system activity during propofol anesthesia. This finding supports that the presynaptic proteins may be related to the mechanism of action of propofol.<br /> (Copyright © 2025 The Author(s). Published by Wolters Kluwer Health, Inc., on behalf of the American Society of Anesthesiologists.) |
|---|---|
| ISSN: | 1528-1175 |
| DOI: | 10.1097/ALN.0000000000005627 |
Full Text Finder
Nájsť tento článok vo Web of Science