ADRA2A(rs1800544)基因多态性在胃肠镜检查中对右美托咪定镇静效果的影响

Effect of ADRA2A (rs1800544) gene polymorphism on sedative effect of dexmedetomidine in gastroenteroscopy

目的观察ADRA2A(rs1800544)基因多态性在胃肠镜检查中对右美托咪定镇静效果的影响,初步探讨右美托咪定镇静效果个体差异的遗传学机制。方法前瞻性选取2020年7月至2021年10月在秦皇岛市中医医院门诊行消化道内镜科检查的125例患者。术前采集所有研究对象外周静脉血,采用PCR-RFLP法进行ADRA2A启动子区域rs1800544基因分型,根据检测结果分为突变纯合型(CC)、突变杂合型(CG)和野生纯合型(GG)。所有患者术前先进行咽部表面麻醉,麻醉完成后开始泵注右美托咪定,负荷剂量0.3μg/kg。从用药开始分别记录所有患者在T1(0 min)、T2(5 min)、T3(10 min)、T4(30 min)、T5(60 min)时刻的心率、平均动脉压(MAP)、血氧饱和度(SpO_(2))等血流动力学指标;采用脑电双频谱指数(BIS)仪监测所有患者BIS值,并根据警觉/镇静评分(OAA/S)标准记录镇静状态评分;比较所有患者术后出现低血压、低血氧、恶心呕吐、头晕、嗜睡、体动等不良反应发生率。结果根据ADRA2A(rs1800544)基因多态性检测报告统计发现,CC型基因48例(38.4%),CG型基因60例(48.0%),GG型基因17例(13.6%)。血流动力学结果显示,3组患者心率、MAP与SpO_(2)在任何时间点差异均无统计学意义(P>0.05);组内比较,与T1时刻相比,在T4、T5时刻心率、MAP值均有所下降,差异均有统计学意义(P<0.05)。BIS结果显示,自T2时刻开始,所有患者的BIS值均开始下降,且在T2、T3、T4、T5时刻,CC组患者的BIS值明显低于CG组和GG组,差异均有统计学意义(P<0.05)。OAA/S评分结果显示,自T3时刻开始,所有患者的OAA/S评分均开始升高,且在T3、T4、T5时刻,CC组患者的OAA/S评分明显高于于CG组和GG组,差异均有统计学意义(P<0.05)。CC组、CG组、GG组不良反应发生率分别为22.92%、23.33%、35.29%,3组之间差异无统计学意义(P>0.05),但CC组分别与CG、GG组相比,不良反应发生率有减少的趋势。结论ADRA2A(rs1800544)基因多态性是造成胃肠镜检查中右美托咪定镇静效果个体差异的遗传因素之一,携带CC型基因的患者对右美托咪定镇静效果更具有敏感性。

Objective To observe the effect of ADRA2A(rs1800544)gene polymorphism on the sedative effect of dexmedetomidine in gastrointestinal endoscopy,and to preliminarily explore the genetic mechanism of individual differences in the sedative effect of dexmedetomidine.Methods From July 2020 to October 2021,125 patients who underwent gastrointestinal endoscopy in the outpatient department of Qinhuangdao Traditional Chinese Medicine Hospital were prospectively selected.The peripheral venous blood was collected from all subjects before surgery,and the ADRA2A promoter region rs1800544 genotyping was performed by PCR-RFLP method.According to the test results,it was divided into mutant homozygous(CC),mutant heterozygous(CG)and wild homozygous(GG).All patients were given pharyngeal topical anesthesia before surgery,and dexmedetomidine was pumped after the anesthesia was completed,with a loading dose of 0.3μg/kg.Record the hemodynamic indexes such as heart rate,mean arterial pressure(MAP)and blood oxygen saturation(SpO_(2))at T1(0 min),T2(5 min),T3(10 min),T4(30 min)and T5(60 min).The BIS values of all patients were monitored by EEG bispectral index(BIS)instrument,and the sedation score was recorded according to the alert/sedation score(OAA/S)standard;the incidences of adverse reactions such as hypotension,hypoxia,nausea and vomiting,dizziness,drowsiness,and physical activity were compared in all patients after operation.Results According to the ADRA2A(rs1800544)gene polymorphism test report statistics,48 cases(38.4%)of CC type gene,60 cases(48.0%)of CG type gene,and 17 cases(13.6%)of GG type gene.The results of hemodynamics showed that there was no statistically significant difference in heart rate,MAP and SpO_(2)of the three groups at any time point(P>0.05);the intra-group comparisons were made,compared with T1,at T4 and T5,the heart rate and MAP values all decreased,the differences were statistically significant(P<0.05).The BIS results showed that from T2,the BIS values of all patients began to decline,and at T2,T3,T4,and T5,the BIS values of patients in the CC group were significantly lower than those in the CG and GG groups,the differences were statistically significant(P<0.05).The OAA/S score results showed that since T3,the OAA/S scores of all patients began to increase,and at T3,T4,and T5,the OAA/S scores of patients in the CC group were significantly higher than those in the CG and GG groups,the differences were statistically significant(P<0.05).The incidences of adverse reactions in the CC group,CG group and GG group were 22.92%,23.33%,and 35.29%,respectively,and there was no statistically significant difference between the three groups(P>0.05),however,compared with the CG and GG groups,the incidence of adverse reactions in the CC group decreased.Conclusion ADRA2A(rs1800544)gene polymorphism is one of the genetic factors that cause individual differences in the sedative effect of dexmedetomidine in gastroenteroscopy,and patients with CC gene are more sensitive to the sedative effect of dexmedetomidine.