Effect Of ?_2A-adrenergic Receptor Gene Polymorphism On Sedative Effect Of Dexmedetomidine

Objectives:Dexmedetomidine,as a commonly used clinical sedative drug,has obvious interpatient variability in its response,which may lead to inadequate treatment and increased side effects.Genetic factors play an important role in individual patient differences,The objectives of this study was to investigate the distribution of?2A-adrenergic receptor?ADRA2A?gene polymorphism in Chinese han populationand its effect on the sedative effect of dexmedetomidine,and to preliminarily explore the genetic mechanism of individual differences in the sedative effect of dexmedetomidine.Methods:One hundred and five patients with American Society of Anesthesiologists?ASA?physical status I and II,undergoing lower extremity surgery under epidural anesthesia were selected.Venous blood was drawn before the operation,the genotypes of ADRA2A C1291G?rs1800544?in the promoter region of the candidate gene was done by PCR-RFLP.Select the L_2/3 gap for epidural catheterization and control the anesthesia plane below T₁₀.Dexmedetomidine infusion was initiated after epidural catheterization,a loading dose of 1?g/kg dexmedetomidine was pumped intravenously with a constant speed for 10 min,the pumping was stopped after a maintenance rate of 0.5?g/?kg·h?for 1hour.From the beginning of infusion until 1 hour later,EEG Bispectral index?BIS?,modified Observer's Assessment of Alertness/Sedation scale?OAA/S scale?,BP,HR,SpO₂ and RR were recorded every 5 minutes.and intraoperative hypotension,bradycardia,respiratory depression and other adverse events also be recoded.Results:Among 105 patients,there were 16 cases of type CC for ADRA2A gene rs1800544 allele,52 cases of CG type and 37 cases of GG type.There was no significant difference in age,BMI and ASA status between the patients with three allele types.The BIS values of all patients began to decrease after 5 minutes of the infusion of dexmedetomidine,in 15-40 minutes,The values of BIS in patients with CG and GG were higher than those in patients with CC?P<0.05?.The modified OAA/S score of all patients began to increase after 30 minutes of the infusion of dexmedetomidine,in 35 to 50minutes,the modified OAA/S scores in patients with CG and GG were lower than those in patients with CC?P<0.05?.There was no significant difference in BIS and modified OAA/S between CG and GG patients at different time points.There was no significant difference in the incidence of BP,HR and adverse events among patients with different gene types.Conclusion:In Chinese Han population,there are three alleles CC,CG and GG at rs1800544 of ADRA2A gene.Compared with patients with CC allele,patients with CG and GG allele have slower sedative response to dexmedetomidine.ADRA2A C1291G gene polymorphism is one of the genetic factors that cause the individual difference of sedative effect of dexmedetomidine.