肾移植病人西罗莫司血药浓度/剂量比与CYP3A5基因多态性的关系

目的:研究肾移植术后病人CYP3A5基因多态性与免疫抑制剂西罗莫司临床个体化给药剂量的关系。方法:采用聚合酶链反应(PCR)和限制性内切片段多态性(RFLP)的方法对105例健康受试者和50例肾移植术后病人进行CYP3A5基因分型。使用高效液相色谱(HPLC)测定病人的西罗莫司血药浓度。比较不同基因型之间的西罗莫司的血药浓度与每千克体重的剂量(C/D)比值的差异。结果:健康受试者和肾移植病人的CYP3A5 A6986G SNPs,CYP3A5*3的发生频率分别为72.9％和71％,差异无显著意义(P>0.05)。肾移植*1/*3型病人的C/D比值(362±s108)μg·L~(-1)per mg·kg~(-1)和*3/*3型病人的C/D比值(375±123)μg·L~(-1)per mg·kg~(-1)差异无显著意义(P>0.05),但两者C/D值均明显高于*1/*1型病人(199±65)μxg·L~(-1)per mg·kg~(-1),差异具有显著意义(P<0.05)。结论:肾移植病人的CYP3A5基因多态性与西罗莫司血药浓度具有相关性,*1/*3型和*3/*3型病人拟取得相似的血药浓度要比*1/*1型病人服用更低剂量的西罗莫司。研究肾移植病人的CYP3A5基因型,有利于肾移植病人术后西罗莫司个体化用药方案的制定。

Relationship between genetic polymorphism of CYP3A5 gene and blood concentration/dose ratio of sirolimus in renal transplant patients

AIM:To study the relationship between genetic polymorphism of CYP3A5 gene and blood concentration/dose ratio of sirolimus in renal transplant patients.METHODS:PCR and RFLP were performed to determine the CYP3A5 genotype of 105 health volunteers and 50 renal transplant patients.Blood samples were collected and the concentration of sirolimus in blood was tested by HPLC.The blood concentration/dose ratio of sirolimus(sirolimus concentration per dose.kg~(-1))was compared among the different genotype.RESULTS:The mutation rate of CYP3A5*3 between health volunteers and patients were 72.9% and 71%(P>0.05).The blood concentration/dose ratio for the patients with*1/*3(362±s 108)μg·L~(-1)per mg·kg~(-1)and *3/*3(375±123)μg·L~(-1)per mg.kg~(-1)were remarkably higher than that of those with*1/*1(199±65)μg·L~(-1)per mg·kg~(-1) (P<0.05).CONCLUSION:The genetic polymorphism of CYP3A5 gene is correlated with the blood concentration/dose ratio of sirolimus.To obtain the similar blood concentration of sirolimus,the patients with *1/*1 should take the drug at a higher dose than those with*1/*3 and *3/*3. Determination of the CYP3A5 genotype is useful for the individualization of medicine in patient after kidney transplantation.