维生素D受体基因多态性对肾移植患者术后早期他克莫司浓度的影响

Influence of Vitamin D Receptor Genetic Polymorphism in Recipients on Concentration of Tacrolimus in the Early Stage After Renal Transplantation

关键词:  肾移植  CYP3A5  维生素D受体  基因多态性  他克莫司  血药浓度  剂量

Key words:  renal transplantation  CYP3A5  vitamin D receptor(VDR)  genetic polymorphism  tacrolimus  drug concentration  dosage

摘要:

目的 研究维生素D受体(vitamin D receptor，VDR)基因多态性对肾移植术后早期他克莫司浓度的影响。方法 以360例使用他克莫司联合霉酚酸类药物以及糖皮质激素三联抗排异方案的肾移植患者为研究对象，检测患者CYP3A5 (rs776746)、VDR(VDR ApaI rs7975232，VDR BsmI rs1544410，VDR FokI rs2228570和VDR TaqI rs731236)基因型，比较分析不同基因型患者肾移植术后7 d时他克莫司血药浓度(concentration，C)、剂量(dose，D)以及浓度剂量比(ratio of concentration to dose，C/D)的差异。结果 CYP3A5非表达组(GG型)患者他克莫司的C和C/D均显著高于CYP3A5表达组(AA和AG型)(P<0.05)。以CYP3A5基因型进行分层后，在CYP3A5非表达组中VDR ApaI rs7975232 AA型患者C/D显著低于AC和CC型患者(P<0.05)，然而在CYP3A5表达组中VDR ApaI rs7975232各基因型的C和C/D差异无统计学意义。此外，无论在CYP3A5表达组还是非表达组中，VDR BsmI rs1544410，VDR TaqI rs731236及VDR FokI rs2228570各基因型之间他克莫司的C、D和C/D差异均无统计学意义。结论 VDR ApaI rs7975232基因多态性与CYP3A5非表达组肾移植患者早期他克莫司血药浓度具有相关性，该基因型检测可能有助于指导肾移植患者他克莫司个体化用药。

Abstract:

OBJECTIVE To investigate the effect of vitamin D receptor(VDR) genetic polymorphism on the concentration of tacrolimus in renal transplant recipients at early stage after transplantation.METHODS The 360 cases of renal transplant recipients who received tacrolimus, mycophenolic acid, and glucocorticoid were recruited. CYP3A5(rs776746) and VDR(VDR ApaI rs7975232, VDR BsmI rs1544410, VDR FokI rs2228570 and VDR TaqI rs731236) genotypes were determined. The differences of concentration(C), dose(D) and the ratio of concentration to dose(C/D) of tacrolimus were compared among all of the genotype groups at the seventh day after renal transplantation. RESULTS The C and C/D of tacrolimus in CYP3A5 non-expresser(GG genotype) were all significantly higher than CYP3A5 expresser(AA and AG genotype)(P<0.05). When taking the different CYP3A5 genotypes in consideration, it was found that the C/D in patients with VDR ApaI rs7975232 AA genotype was significantly lower than those with AC and CC genotypes for CYP3A5 non-expresser(P<0.05). However, VDR ApaI rs7975232 gene polymorphism had no influence on C and C/D of tacrolimus in CYP3A5 expresser. Besides, no matter in CYP3A5 expresser or in non-expresser, VDR BsmI rs1544410, VDR TaqI rs731236 and VDR FokI rs2228570 had no effect on C, D and C/D of tacrolimus. CONCLUSION During the early stage of renal transplantation, the polymorphism of VDR ApaI rs7975232 show significant relevance with tacrolimus concentration in CYP3A5 non-expresser. The detection of the genotype might be helpful to guide individual therapy.