新疆多民族UGT1A9基因多态性与丙泊酚血药浓度相关性

Correlation between UGT1A9 gene polymorphism and propofol concentration in Xinjiang

目的:探讨新疆多民族患者尿苷二磷酸葡萄糖醛酸转移酶(UGT)1A9基因多态性与丙泊酚血药浓度的相关性。方法:选取2019年12月至2021年3月新疆医科大学附属肿瘤医院102例多民族患者,采用气-质联用(LC-MS)法检测患者5个时间点,即麻醉诱导前(T0)、睫毛反射消失前(T1)、血浆清除率至40~50 L·kg^(-1)·h^(-1)时(T2)、停药即刻(T3)和停药后30 min时(T4)外周血中丙泊酚的血药浓度。同时提取患者外周血DNA,采用基质辅助激光解吸电离飞行时间质谱(MAL-DI-TOF-MS)法检测对UGT1A9(rs 2741049、rs 3806598、rs 6731242、rs 3832043)4个基因位点进行基因多态性检测。统计基因分型结果,将影响血药浓度的所有因素进行单因素分析。结果:rs 2741049,rs 3806598,rs 6731242,rs 3832043四个位点基因型频率均符合Hardy-Weinberg平衡(P>0.05)。其中rs 3806598位点A/A型汉族与其他民族基因分布比较,差异有统计学意义(P<0.05),其他位点各民族基因型分布均差异均无统计学意义(P>0.05)。T0、T1、T2共3个时刻rs 3806598位点A/A型各民族血药浓度差异无统计学意义,T3、T4两个时刻血药浓度汉族较维吾尔族和其他民族差异有统计学意义(P<0.05)。单因素分析结果表明,不同民族、身高、体质量、吸烟、饮酒、出血量等因素都对患者体内丙泊酚的代谢具有影响(P<0.05)。结论:新疆多民族患者UGT1A9基因rs 3806598位点基因分布存在差异且与丙泊酚的血药浓度相关,民族、身高、体质量、吸烟、饮酒、出血量等因素都对患者体内丙泊酚的代谢具有影响应在临床麻醉中斟酌用药。

OBJECTIVE To investigate the correlation between the polymorphism of uridine diphosphate glucuronosyltransferase(UGT)1A9 gene and the plasma concentration of propofol in multi-ethnic patients in Xinjiang.METHDOS From December 2019 to March 2021,102 multi-ethnic patients were selected from the Cancer Hospital Affiliated to Xinjiang Medical University.Gas chromatography-mass spectrometry(LC-MS)was used to detect the concentration of propofol in peripheral blood at five time points,i.e.,before anesthesia induction(T0),before disappearance of eyelash reflex(T1),when the total plasma clearance rate reached 40~50 L·kg^(-1)·h^(-1)(T2),immediately after drug discontinuation(T3)and 30 min after drug discontinuation(T4).At the same time,DNA was extracted from peripheral blood of the patient,and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry(MAL-DI-TOF-MS)was used to detect gene polymorphisms at four gene loci of UGT1A9(rs2741049,rs3806598,rs6731242,and rs3832043).Statistical analysis of genotyping results revealed that all the factors affecting the serum drug concentration were subject to single factor analysis.RESULTS Genotypic frequencies of rs 2741049,rs3806598,rs6731242 and rs3832043 were in accordance with Hardy-Weinberg equilibrium(P>0.05).Among them,the gene distribution of A/A Han nationality at rs3806598locus was statistically different from that of other nationalities(P<0.05),and the genotype distribution of all nationalities at other loci was not statistically different(P>0.05).There was no significant difference in the blood drug concentration of A/A ethnic groups at rs3806598 locus among the three time points of T0,T1and T2.The blood drug concentration in Han nationality at T3and T4was different from that in Uyghur nationality and other ethnic groups(P<0.05).The results of univariate analysis showed that different ethnic groups,height,weight,smoking,alcohol consumption,and bleeding volume all had effects on the metabolism of propofol in patients(P<0.05).CONCLUSION The gene distribution at rs3806598locus of UGT1A9 gene in Xinjiang multi-ethnic patients is different and is related to the blood concentration of propofol.Nationality,height,weight,smoking,alcohol consumption,and bleeding volume all have effects on the metab-olism of propofol in patients.Medication should be considered in clinical anesthesia.