中国肾移植病人西罗莫司基因多态性研究

Immunosuppressive strategies and management

目的研究肾移植术后病人MDR1和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例肾移植术后的病人进行MDR1和CYPA5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公斤体重的剂量比值(c/D)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%;MDR1 C3435T SNPs的发生频率分别为51.0%和44.0%,差异均无显著意义(P>0.05)。肾移植*1/*3型病人的c/D比(362±108)μg·L^(-1)per mg·kg^(-1)和*3/*3型病人的c/D比(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)μg·L^(-1) per mg·kg^(-1),差异具有显著意义(P<0.05)。而MDR1不同基因型对c/D的差异无显著意义。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。

Advances in immunosuppressive therapy have significantly improved short-term allograft and patient survival. However, chronic allograft failure, antibody mediated rejection, recurrent diseases and immunosuppressive drug associated adverse effects remain serious barriers to long-term survival and quality of life. New immunosuppressive agents and protocols are being evaluated to combat these problems. Importantly, clinicians must work to manage post-transplant complications and avoid complex medication regimens, which will potentiate drug interactions and non-compliance.