Associations between SNAP-25 gene polymorphism, autonomic nervous system activity and recovery of consciousness from propofol anesthesia

Background: The release of synaptic neurotransmitters and function of pre-synaptic 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 pre-synaptic proteins comprising the 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 BIS, heart rate variability (HRV), and peripheral perfusion index (PPI) were explored, based on the polymorphic site of significant differences in consciousness. Results: The 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 (259-378) vs. 379 (318-466) 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 ( χ 2 = 11.916, P=0.008). Other consciousness indices, Ce, HRV and PPI, 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 pre-synaptic proteins may be related to the mechanism of action of propofol.