基因多态性对慢性肾脏病患者罗沙司他疗效的影响  

Influence of gene polymorphism on efficacy of roxadustat in patients with chronic kidney disease

作　　者：陈奎 马爽[1] 张丽洁 蒲薪羽 武彤 杨晶[2] 赵占正[1] 肖静[1] CHEN Kui;MA Shuang;ZHANG Lijie;PU Xinyu;WU Tong;YANG Jing;ZHAO Zhanzheng;XIAO Jing(Deparement of Nephrology,The First Affiliated Hospital of Zhengzhou University,Zhengzhou 450000,China;Deparement of Pharmacy,The First Affiliated Hospital of Zhengzhou University,Zhengzhou 450000,China)

机构地区：[1]郑州大学第一附属医院肾脏内科,郑州450000 [2]郑州大学第一附属医院药学部,郑州450000

出　　处：《肾脏病与透析肾移植杂志》2022年第2期133-138,共6页Chinese Journal of Nephrology,Dialysis & Transplantation

摘　　要：目的:通过观察慢性肾脏病患者细胞色素酶(CYP2C8)及尿苷二磷酸葡萄糖醛酸基转移酶(UGT1A9)基因型,与罗沙司他谷浓度和血红蛋白反应率的关系,探究基因多态性对罗沙司他代谢及贫血疗效的影响。方法:纳入22例未进入透析治疗、合并肾性贫血的慢性肾脏病患者,通过聚合酶链反应-限制性片段长度多态性(PCR-RFLP)法检测患者基因型,并检测患者罗沙司他治疗4~8周时的血红蛋白浓度,将血红蛋白较基线值升高≥10 g/L定义为“血红蛋白反应”,以评价罗沙司他的疗效。应用液相色谱-串联质谱(LC-MS/MS)法检测罗沙司他谷浓度,对比各基因型组患者药物谷浓度差异。分析不同基因分组患者及不同疗效患者间的药物谷浓度差异。结果:UGT1A9 rs2070959位点AA型患者治疗后血红蛋白升高值及罗沙司他谷浓度均低于AG型(P<0.05),但两组血红蛋白反应率差异无统计学意义。UGT1A9 rs3832043位点各基因型组患者治疗前后血红蛋白升高值、血红蛋白反应率、平均谷浓度差异均无统计学意义。CYP2C8相关位点未检测出不同基因型。血红蛋白反应组患者罗沙司他谷浓度显著高于无反应组(P<0.05)。结论:UGT1A9基因多态性显著影响罗沙司他的贫血疗效及药物谷浓度。罗沙司他的贫血疗效与药物谷浓度有关。Objective:By exploring relationship among CYP2 C8(cytochrome enzyme)and UGT1 A9(uridine diphosphate glucuronyltransferase)genotypes,roxadustat trough concentration and hemoglobin response rate in patients with chronic kidney disease,analyse effect of gene polymorphisms on metabolism of roxadustat and efficacy of anemia.Methodology:Twenty-two chronic kidney disease patients not receiving dialysis and complicated with renal anemia were enrolled.The genotypes were detected by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)method.The hemoglobin concentration of patients after roxadustat treatment for 4~8 weeks was measured,and an increase in hemoglobin of≥10 g/L from the baseline value was defined as“hemoglobin response”.The trough concentrations of roxadustat were detected by liquid chromatography-tandem mass spectrometry(LC-MS/MS),and the differences in drug trough concentrations of patients in each genotype group were compared.Drug trough concentrations of patients with different genotype and different efficacy were analyzed.Results:The elevated hemoglobin values and rosalostat concentrations in UGT1 A9 rs2070959 locus AA group were significantly lower than that in AG group(P<0.05),but there was no difference in hemoglobin response rate between the two groups(P>0.05).There was no significant difference in hemoglobin elevation before and after treatment,hemoglobin response rate,and mean trough concentration between UGT1 A9 rs3832043 locus genotype groups(P>0.05).No different genotypes were detected at CYP2 C8-related loci.The trough concentration of roxadustat in hemoglobin response group was significantly higher than that in non-response group(P<0.05).Conclusion:UGT1 A9 gene polymorphism significantly affects efficacy and trough concentration of roxadustat.The anemic efficacy of roxadustat is related to trough concentration of drug.

关 键 词：肾性贫血 罗沙司他 基因多态性 

分 类 号：R692[医药卫生—泌尿科学]