ABCB1、CYP2B6基因多态性对丙泊酚血药浓度的影响

Effect of ABCB1 and CYP2B6 Gene Polymorphism on Propofol Plasma Concentration

目的:探讨药物转运体ABCB1 C3435T与药物代谢酶CYP2B6 G516T基因多态性对丙泊酚血药浓度的影响,为丙泊酚临床个体化给药提供实验室数据。方法:采用荧光染色原位杂交法(FISH),进行ABCB1 C3435T和CYP2B6 G516T基因多态性检测,用高效液相-荧光法检测血药浓度。根据不同基因型患者使用丙泊酚麻醉后30,60 min给药总量,比较基因多态性与丙泊酚标准化血药浓度的关系。结果:丙泊酚持续给药30 min时,ABCB1 C3435T三种基因型患者给药总量和标准血药浓度比较,差异无统计学意义(P>0.05);丙泊酚持续给药60 min时,ABCB1不同基因型患者给药总量有明显差异(P<0.05),ABCB1 C3435T野生纯合子CC基因型患者给药总量高于变异型(CT/TT)患者。给药60 min时,4组患者给药总量差异有统计学意义(P<0.05)。不同CYP2B6 G516T基因型患者在丙泊酚持续给药30 min和60 min时,给药总量和标准血药浓度无相关性。结论:ABCB1 C3435T基因多态性对丙泊酚血药浓度有影响,野生型患者为达到相同的血药浓度需要提高给药剂量。

Objective:To investigate the effect of drug transporter ABCB1 C3435T and drug-metabolizing enzyme CYP2B6 G516T gene polymorphism on propofol plasma concentration to provide laboratory data for clinical individualized administration of propofol.Methods:Polymorphism detection of ABCB1 C3435T and CYP2B6 G516T gene was performed by fluorescence staining in situ hybridization(FISH),and the blood concentration of propofol was detected by high performance liquid phase-fluorescence.The total dose of ABCB1 C3435T genotypes was determined at 30 minutes and 60 minutes of propofol anesthesia administered to patients with different genotypes to investigate the correlation between the gene polymorphism and propofol standardized plasma concentration.Results:There was no correlation between the total dose of ABCB1 C3435 T genotypes and the standard plasma concentration when propofol was administered for 30 minutes.When propofol was administered for 60 minutes,the total dose of ABCB1 genotypes was different(P<0.05),and the total dose of ABCB1 C3435T wild homozygous CC genotype was higher than that of variant(CT/TT)patients after 60-minute administration,and there was a significant difference among the four groups in the total dosage(P<0.05).Conclusion:ABCB1 C3435T gene polymorphism has an effect on the plasma concentration of propofol,and the wild-type patient needs to increase the dose to achieve the same blood concentration.