CYP3A5*3基因多态性对儿童难治性肾病综合征患者他克莫司血药浓度/剂量比的影响研究

Study on the influence of CYP3A5*3 genetic polymorphisms on serum tacrolimus concentration/dose ratio in children with refractory nephrotic syndrome

目的探讨CYP3A5*3基因多态性对儿童难治性肾病综合征患者他克莫司血药浓度/剂量比的影响。方法选取2020年1月1日~2021年12月31日在徐州医科大学附属医院就诊的儿童难治性肾病综合征患者71例,给药后1周采用酶放大免疫测定法检测他克莫司血药谷浓度(C_(0)),与每千克日剂量(D)相比计算C_(0)/D;采用Sanger法测定患者CYP3A5*3基因型,并分析基因型对患者他克莫司浓度/剂量比的影响,为他克莫司的个体化治疗提供基因导向的药理学依据。结果CYP3A5*1/*1基因型组他克莫司C_(0)/D值为68.27±40.51,显著低于*1/*3基因型组的112.29±55.25和*3/*3基因型组的176.98±86.55。结论CYP3A5*3基因多态性是影响儿童难治性肾病综合征患者他克莫司C_(0)/D值的遗传因素,基因型为CYP3A5*1/*1的患者在达到相同目标的血药浓度时可能需要更高的剂量;用药前进行基因型检测能够更有效地指导他克莫司的个体化应用。

Objective To explore CYP3A5*3 genetic polymorphisms on tacrolimus concentration/dose ratio in children with refractory nephropathy syndrome(RNS).Methods Seventy-one children with RNS who were admitted to the Affiliated Hospital of Xuzhou Medical University from January 1,2020 to December 31,2021 were selected.Serum trough concentration of tacrolimus was determined by enzyme amplification immunoassay one week after administration(C_(0)),and C_(0)/D ratio was calculated(D:a daily dose per kilogram).CYP3A5*3 genotype was determined by Sanger method.The influence of genotype on tacrolimus concentration/dose ratio was analyzed to provide pharmacogenetic basis for gene-oriented individualized treatment.Results C 0/D of tacrolimus in CYP3A5*1/*1 genotype group was 68.27±40.51,significantly lower than 112.29±55.25 in*1/*3 genotype group and 176.98±86.55 in*3/*3 genotype group.Conclusion CYP3A5*3 genetic polymorphism is a genetic factor affecting tacrolimus C_(0)/D in children with refractory nephrotic syndrome,and patients with the CYP3A5*1/*1 genotype may need a higher dose to achieve the same target blood concentration;genotypic testing before administration may guide the clinical individualized application of tacrolimus more effectively.