目的建立快速检测CYP3A5基因型的新方法及其临床应用。方法针对CYP3A5不同基因型特异性位点设计引物,采用等位基因特异性PCR方法(Allele specific PCR,AS-PCR)进行扩增,通过琼脂糖凝胶电泳分辨不同基因型,并检测临床标本100例,与一代测...目的建立快速检测CYP3A5基因型的新方法及其临床应用。方法针对CYP3A5不同基因型特异性位点设计引物,采用等位基因特异性PCR方法(Allele specific PCR,AS-PCR)进行扩增,通过琼脂糖凝胶电泳分辨不同基因型,并检测临床标本100例,与一代测序法比对两个方法的一致率。结果新方法检测100例临床标本中,CYP3A5基因型*1/*1型15例;*1/*3型26例;*3/*3型59例,结果与一代测序法一致,一致率100%。结论通过AS-PCR检测CYP3A5基因型,操作简便,结果易于判断,可应用于临床。展开更多
BACKGROUND Tacrolimus(TAC)is metabolized primarily by the CYP3A-encoded enzyme family(CYP3A4,CYP3A5,and CYP3A7).Individuals expressing the CYP3A51 allele are considered fast metabolizers and generally require higher T...BACKGROUND Tacrolimus(TAC)is metabolized primarily by the CYP3A-encoded enzyme family(CYP3A4,CYP3A5,and CYP3A7).Individuals expressing the CYP3A51 allele are considered fast metabolizers and generally require higher TAC doses to reach therapeutic levels.AIM To evaluate the predictive value of the TAC concentration-to-dose(C0/D)ratio for identifying CYP3A5 poly-morphisms in renal transplant recipients.METHODS Eighty-six de novo kidney transplant recipients with TAC-based immunosuppression from the Department of Nephrology and Dialysis at Military Hospital 103(Hanoi,Vietnam)were included in this retrospective study.Blood samples were collected within the first week post-transplantation to monitor TAC levels and to perform genotyping for CYP3A5 genetic polymorphisms.RESULTS The CYP3A53/3 genotype was identified in 37 patients(43%),CYP3A51/3 in 40 patients(46.5%),and CYP3A51/1 in 9 patients(10.5%).Patients carrying the CYP3A51/3 or CYP3A51/1 genotype,classified as fast metabolizers(CYP3A5 expressers),had significantly lower TAC C0 concentrations and C0/D ratios compared to slow meta-bolizers(CYP3A53/3 genotype)at multiple time points during follow-up(all P<0.001).Notably,the TAC C0/D ratio obtained on day 1(0.91)was shown to predict CYP3A5 polymorphism with a sensitivity of 84.6%and a specificity of 84.6%.CONCLUSION This study demonstrates that the TAC C0/D ratio provides a reliable predictive value for CYP3A5 polymorphisms,which can be used to individualize TAC dosing in renal transplant recipients in Vietnam and other low-income countries.展开更多
目的观察CYP3A5基因多态性对肾移植受者术后早期他克莫司（tacrolimus，Tac）浓度/剂量比值（blood drug concentration/dose，C/D）的影响，探讨适合不同基因型受者的Tac起始剂量。方法按CYP3A5基因型将157例肾移植受者分为表达组（CYP...目的观察CYP3A5基因多态性对肾移植受者术后早期他克莫司（tacrolimus，Tac）浓度/剂量比值（blood drug concentration/dose，C/D）的影响，探讨适合不同基因型受者的Tac起始剂量。方法按CYP3A5基因型将157例肾移植受者分为表达组（CYP3A5*1/*1型和CYP3A5*1/*3型患者，72例）、不表达组（CYP3A5*3/*3型患者，85例）。比较不同基因型患者之间术后Tac C/D比值、急性排斥反应与药物不良反应的发生率；记录不同基因型患者起始Tac剂量及达到肾移植术后早期有效目标药物浓度（7～14μg/L）的间隔时间。结果 CYP3A5表达组患者术后7、14、30天的C/D比值均低于不表达组（均P＜0.05），术后1个月组间急性排斥反应发生率差异无统计学意义（P＞0.05），而不表达组药物不良反应发生率高于表达组（P＜0.05）；表达组及不表达组患者术后起始剂量无明显差异（分别为0.129、0.132 mg/kg，P＞0.05）。但表达组患者达到目标浓度时间较不表达患者明显缩短（P＜0.05）。结论受CYP3A5基因多态性影响，*1/*1和*1/*3型患者早期要达到目标血药浓度，需提高该组患者的起始用药剂量，而*3/*3型患者则应适当降低起始剂量。根据CYP3A5基因多态性作为Tac个体化用药的依据，可以减少早期急性排斥反应及不良反应发生率，提高肾移植的临床效果。展开更多
文摘目的建立快速检测CYP3A5基因型的新方法及其临床应用。方法针对CYP3A5不同基因型特异性位点设计引物,采用等位基因特异性PCR方法(Allele specific PCR,AS-PCR)进行扩增,通过琼脂糖凝胶电泳分辨不同基因型,并检测临床标本100例,与一代测序法比对两个方法的一致率。结果新方法检测100例临床标本中,CYP3A5基因型*1/*1型15例;*1/*3型26例;*3/*3型59例,结果与一代测序法一致,一致率100%。结论通过AS-PCR检测CYP3A5基因型,操作简便,结果易于判断,可应用于临床。
基金Supported by the Vietnam National Foundation for Science and Technology Development,No.NAFOSTED 04/2020/TN.
文摘BACKGROUND Tacrolimus(TAC)is metabolized primarily by the CYP3A-encoded enzyme family(CYP3A4,CYP3A5,and CYP3A7).Individuals expressing the CYP3A51 allele are considered fast metabolizers and generally require higher TAC doses to reach therapeutic levels.AIM To evaluate the predictive value of the TAC concentration-to-dose(C0/D)ratio for identifying CYP3A5 poly-morphisms in renal transplant recipients.METHODS Eighty-six de novo kidney transplant recipients with TAC-based immunosuppression from the Department of Nephrology and Dialysis at Military Hospital 103(Hanoi,Vietnam)were included in this retrospective study.Blood samples were collected within the first week post-transplantation to monitor TAC levels and to perform genotyping for CYP3A5 genetic polymorphisms.RESULTS The CYP3A53/3 genotype was identified in 37 patients(43%),CYP3A51/3 in 40 patients(46.5%),and CYP3A51/1 in 9 patients(10.5%).Patients carrying the CYP3A51/3 or CYP3A51/1 genotype,classified as fast metabolizers(CYP3A5 expressers),had significantly lower TAC C0 concentrations and C0/D ratios compared to slow meta-bolizers(CYP3A53/3 genotype)at multiple time points during follow-up(all P<0.001).Notably,the TAC C0/D ratio obtained on day 1(0.91)was shown to predict CYP3A5 polymorphism with a sensitivity of 84.6%and a specificity of 84.6%.CONCLUSION This study demonstrates that the TAC C0/D ratio provides a reliable predictive value for CYP3A5 polymorphisms,which can be used to individualize TAC dosing in renal transplant recipients in Vietnam and other low-income countries.
