Vavić Neven, Rančić Nemanja, Cikota-Aleksić Bojana, Magić Zvonko, Cimeša Jelena, Obrenčević Katarina, Radojević Milorad, Mikov Momir, Dragojević-Simić Viktorija
Vojnosanit Pregl. 2016 Jul;73(7):663-7. doi: 10.2298/VSP150505016V.
BACKGROUND/AIM: Polymorphisms of genes which encode transporter P-glycoprotein and most important enzymes for tacrolimus pharmacokinetics can have significant influence reflecting on blood concentrations of this drug. The aim of this study was to examine the distribution of polymorphisms of CYP3A5, CYP3A4 and ABCB1 genes in patients subjected to renal transplantation, for the first time in our transplantation center.
The research was designed as a prospective cross-sectional study which included 211 patients subjected to renal transplantation in the Centre for Solid Organ Transplantation of the university tertiary health care hospital, Military Medical Academy, Belgrade, Serbia. Patients of both genders, 22−69-year-old, Caucasians, subjected to immunosuppressive regimen, including tacrolimus, were recruited for the study. CYP3A5 6986A>G (the *3 or *1, rs776746), CYP3A4 - 392A>G (the *1 or *1B, rs2740574) and ABCB1 3435C>T (rs1045642) genotypes were determined by TaqMan® SNP genotyping assays.
Most of our patients (94.8%) had functional CYP3A4 enzyme, while 87.7% of all the patients had diminished CYP3A5 enzymatic activity. On the other hand, about one third of them, 31.3%, had functional ABCB1 transporter.
A total of 84.8% of our patients were found to express both the CYP3А533 genotype (associated with diminished CYP3А5 enzymatic activity) and CYP3А411/11B (associated with functional CYP3А4 enzymatic activity), while out of all the patients with diminished CYP3A5 enzymatic activity, 68.7% had diminished activity of ABCB1 transporter. However, further studies are necessary in order to show the influence of these genetic polymorphisms on tacrolimus blood concentrations in patients after renal transplantation.
背景/目的：编码转运蛋白P-糖蛋白以及参与他克莫司药代动力学的最重要酶类的基因多态性，可能对该药物的血药浓度产生显著影响。本研究的目的是在我们的移植中心首次检测肾移植患者中CYP3A5、CYP3A4和ABCB1基因多态性的分布情况。
本研究设计为前瞻性横断面研究，纳入了塞尔维亚贝尔格莱德军事医学科学院大学三级医疗保健医院实体器官移植中心的211例肾移植患者。招募年龄在22 - 69岁、高加索人种、接受包括他克莫司在内的免疫抑制方案的男女患者参与研究。通过TaqMan® SNP基因分型检测法确定CYP3A5 6986A>G（3或1，rs776746）、CYP3A4 - 392A>G（1或1B，rs2740574）和ABCB1 3435C>T（rs1045642）基因型。
我们的大多数患者（94.8%）具有功能性CYP3A4酶，而所有患者中有87.7%的CYP3A5酶活性降低。另一方面，约三分之一的患者（31.3%）具有功能性ABCB1转运蛋白。
我们共发现84.8%的患者同时表达CYP3А533基因型（与CYP3А5酶活性降低相关）和CYP3А411/11B（与功能性CYP3А4酶活性相关），而在所有CYP3A5酶活性降低的患者中，68.7%的患者ABCB1转运蛋白活性降低。然而，为了阐明这些基因多态性对肾移植患者他克莫司血药浓度的影响，还需要进一步的研究。
