安徽地区CHF患者CYP3A4^(*)18B和CYP3A5^(*)3基因多态性分布及其对地高辛血药浓度的影响  

Distribution of CYP3A4^(*)18B and CYP3A5^(*)3 Gene Polymorphisms and its Effects on Serum Concentration of Digoxin in Patients with CHF in Anhui Province

作　　者：胡娟[1] 孟祥云[1] 冯俊[2] 周高亮[2] 汪星辉[1] 高玉[2] Hu Juan;Meng Xiangyun;Feng Jun;Zhou Gaoliang;Wang Xinghui;Gao Yu(Department of Pharmacy,Hefei Second People's Hospital/Hefei Hospital Affiliated to Anhui Medical University,Hefei 230011,China;Department of Cardiology,Hefei Second People's Hospital/Hefei Hospital Affiliated to Anhui Medical University,Hefei 230011,China)

机构地区：[1]合肥市第二人民医院/安徽医科大学附属合肥医院药学部,合肥230011 [2]合肥市第二人民医院/安徽医科大学附属合肥医院心内科,合肥230011

出　　处：《中国药师》2022年第2期267-272,共6页China Pharmacist

基　　金：安徽医科大学自然科学基金项目(编号:2019xkj092);蚌埠医学院自然科学基金项目(编号:BYKY2019302ZD);合肥市第二人民医院科研项目(编号:20194551);合肥市第二人民医院光华青年基金项目(编号:20191718)。

摘　　要：目的:观察安徽地区心力衰竭(CHF)患者CYP3A4^(*)18B和CYP3A5^(*)3基因多态性分布情况及其对地高辛血药浓度的影响。方法:收集92例安徽地区汉族CHF患者的血液样本,进行地高辛治疗药物浓度监测(TDM),并采用PCR-荧光探针技术检测CYP3A4^(*)18B和CYP3A5^(*)3基因多态性。结果:安徽地区汉族CHF患者CYP3A4^(*)18B的3种基因型分布为^(*)18/^(*)18(0%),^(*)1/^(*)18(0%),^(*)1/^(*)1(100%),CYP3A5^(*)3三种基因型分布分别为^(*)3/^(*)3(61.9%),^(*)1/^(*)3(29.4%),^(*)1/^(*)1(8.7%)。CYP3A4^(*)18B中^(*)1/^(*)1组的地高辛血药浓度为(1.29±0.86)μg·L^(-1),CYP3A5^(*)3中^(*)3/^(*)3组、^(*)1/^(*)3组和^(*)1/^(*)1组对应的地高辛血药浓度分别为(1.53±0.92)μg·L^(-1)、(1.12±0.59)μg·L^(-1)和(0.65±0.29)μg·L^(-1),差异均有统计学意义(P<0.05),而在不同性别中CYP3A4^(*)18B和CYP3A5^(*)3不同基因型对应的地高辛血药浓度差异无统计学意义(P>0.05)。结论:安徽地区92例CHF患者中CYP3A4^(*)18B和CYP3A5^(*)3基因型分别以^(*)1/^(*)1和^(*)3/^(*)3型为主,其中CYP3A5^(*)3基因多态性可影响地高辛血药浓度。Objective:To observe the distribution of CYP3A4^(*)18B and CYP3A5^(*)3 gene polymorphisms in patients with heart failure(CHF)in Anhui province and its effects on the blood concentration of digoxin.Methods:Blood samples of 92 Han patients with CHF in Anhui province were collected for digoxin therapeutic drug monitoring(TDM)from May 2020 to May 2021.The polymorphisms of CYP3A4^(*)18B and CYP3A5^(*)3 genes were detected by PCR-fluorescent probe technology.Results:The three genotypes of CYP3A4^(*)18B in Han patients with CHF in Anhui were^(*)18/^(*)18(0%),^(*)1/^(*)18(0%)and^(*)1/^(*)1(100%),and those of CYP3A5^(*)3 were^(*)3/^(*)3(61.9%),^(*)1/^(*)3(29.4%)and^(*)1/^(*)1(8.7%).The plasma concentration of digoxin in^(*)1/^(*)1 group of CYP3A4^(*)18B was(1.29±0.86)μg·L^(-1),the corresponding plasma concentration of digoxin in^(*)3/^(*)3 group,^(*)1/^(*)3 group and^(*)1/^(*)1 group of CYP3A5^(*)3 respectively was(1.53±0.92)μg·L^(-1),(1.12±0.59)μg·L^(-1)and(0.65±0.29)μg·L^(-1),and the differences were statistically significant(P<0.05).There was no significant difference in serum concentration of digoxin corresponding to different genotypes of CYP3A4^(*)18B and CYP3A5^(*)3 in different genders(P>0.05).Conclusion:CYP3A4^(*)18B and CYP3A5^(*)3 genotypes are mainly^(*)1/^(*)1 and^(*)3/^(*)3 genotypes respectively in 92 patients with CHF in Anhui province.CYP3A5^(*)3 gene polymorphism can affect the serum concentration of digoxin.

关 键 词：地高辛 血药浓度 基因多态性 CYP3A4^(*)18B CYP3A5^(*)3 

分 类 号：R968[医药卫生—药理学]