CYP3A4*1G基因多态性对醋酸亮丙瑞林微球治疗体外受精胚胎移植术(IVF)患者血药浓度的影响  

Effect of CYP3A4*1G gene polymorphism on serum concentration of leuprelin acetate microspheres in vitro fertilization embryo transfer(IVF)patients

作　　者：李丽华 吕佳燕 迪娜热尔·迪力达西 陈艳梅 郭鑫 LI Lihua;LV Jiayan;DI NAREER Dilidaxi;CHEN Yanmei;GUO Xin(Department of Pharmacy,Maternal and Child Care Service Center of Urumqi,Urumqi,Xinjiang,China,830011;Department of Reproductive Medicine,Maternal and Child Care Service Center of Urumqi,Urumqi,Xinjiang,China,830011)

机构地区：[1]乌鲁木齐市妇幼保健院药剂科,新疆乌鲁木齐830011 [2]乌鲁木齐市妇幼保健院辅助生殖科,新疆乌鲁木齐830011

出　　处：《分子诊断与治疗杂志》2024年第11期2059-2063,2068,共6页Journal of Molecular Diagnostics and Therapy

基　　金：新疆维吾尔自治区“青年科技人才⁃乡村振兴”项目(WJWY⁃XCZX202225)。

摘　　要：目的探讨CYP3A4*1G基因多态性对醋酸亮丙瑞林微球治疗体外受精⁃胚胎移植术(IVF)患者血药浓度的影响。方法选取2022年3月至12月在乌鲁木齐市妇幼保健院使用醋酸亮丙瑞林微球药物降调治疗的体外受精⁃胚胎移植(IVF⁃ET)的45例不孕症患者为研究对象,通过PCR和Sanger测序技术检测CYP3A4*1G基因单核苷酸多态性,使用超高效液相色谱⁃质谱联用(UPLC⁃MS/MS)法检测患者用药后血清中醋酸亮丙瑞林微球的血药浓度,分析基因单核苷酸多态性与醋酸亮丙瑞林微球血药浓度、患者激素水平之间的关系。结果建立人血清中的醋酸亮丙瑞林微球标准曲线方程:Y=1.879*e^(⁃2)*X+3.352*e^(⁃4)(R^(2)=0.9993),经验证醋酸亮丙瑞林微球在0.1~100 ng/mL浓度范围呈良好的线性关系。CYP3A4*1G不同基因分型患者在使用醋酸亮丙瑞林微球治疗后不同时间点血清醋酸亮丙瑞林微球血药浓度比较差异无统计学意义(P>0.05)。但CYP3A4*1G不同基因型患者使用醋酸亮丙瑞林微球治疗后激素指标变化情况有所差异,黄体生成激素(LH)、雌二醇(E2)激素水平在不同基因型中比较差异有统计学意义(P<0.05)。结论研究建立的超高效液相色谱⁃质谱联用法准确、可靠,可用于醋酸亮丙瑞林微球在人体内血药浓度的测定。CYP3A4*1G基因多态性与醋酸亮丙瑞林微球治疗后患者LH、E2激素水平有一定的相关性。Objective To investigate the effect of CYP3A4*1G gene polymorphism on the pharmacodynamics and efficacy of leuprelin acetate microspheres in vitro fertilization⁃embryo transfer(IVF)pa⁃tients.Methods A total of 45 infertility patients who underwent leuprelin downregulation treatment for in vi⁃tro fertilization and embryo transfer(IVF⁃ET)at Urumqi Maternal and Child Health Hospital from March to December 2022 were selected as the study subjects.The single nucleotide polymorphism of the CYP3A4*1G gene was detected using PCR and Sanger sequencing technology.Ultra⁃high⁃performance liquid chromatogra⁃phy⁃mass spectrometry(UPLC⁃MS/MS)was used to detect the blood concentration of leuprelin acetate microspheres in the serum of patients after treatment.The relationship between gene single nucleotide polymorphism,blood concentration of leuprelin acetate microspheres,and hormone levels of patients was analyzed.Results The standard curve equation for leuprelin acetate microspheres in human serum was determined to be Y=1.879*e^(⁃2)*X+3.352*e^(⁃4)(R^(2)=0.9993).It was demonstrated that leuprelin acetate microspheres exhibited a strong linear relationship within the concentration range of 0.1~100 ng/mL.There was no significant difference in serum leuprelin acetate microspheres concentration among patients with varying genotypes of CYP3A4*1G following treatment with leuprelin acetate microspheres at different time points(P>0.05).However,when patients with different genotypes of CYP3A4*1G were treated with leuprelin acetate microspheres,the levels of luteinizing hormone(LH)and estradiol(E2)varied significantly across genotypes(P<0.05).Conclusion The ultra⁃high performance liquid chromatography⁃mass spectrometry method is accurate and reliable,making it suitable for determining the concentration of leuprelin acetate microspheres in human blood.The CYP3A4*1G gene polymorphism was found to be correlated with LH and E2 hormone levels in patients undergoing treatment with leuprelin acetate microspheres.

关 键 词：CYP3A4*1G 醋酸亮丙瑞林微球 不孕 体外受精⁃胚胎移植 血药浓度 

分 类 号：R969.1[医药卫生—药理学]