a Department of Medical Biology, Istanbul Faculty of Medicine , Istanbul University , Istanbul , Turkey.
b Department of Nephrology , Istanbul Faculty of Medicine, Istanbul University , Istanbul , Turkey.
Ren Fail. 2018 Nov;40(1):395-402. doi: 10.1080/0886022X.2018.1489285.
There are differences in pharmacokinetic of mycophenolic acid among individuals. The UGT1A9 enzyme is of special interest since it is the main enzyme involved in the glucuronidation of MPA. Single nucleotide polymorphisms in the UGT1A9 gene may be responsible for individual differences in the pharmacokinetics of MPA. The aim of this study was to explain MPA pharmacokinetics in UGT1A9 1399 C > T polymorphisms in Turkish renal transplant patients.
One hundred and twenty-five living-donor transplant recipients and 100 healthy control subjects underwent UGT1A9 1399 C > T genotyping using polymerase chain reaction-restriction fragment length polymorphism. Concentrations of MPA were determined with Cloned Enzyme Donor Immunoassay (CEDIA). Besides that, all the patients were monitored for acute rejection and graft function during the study period.
The UGT1A9 1399 C > T CC, CT, and TT genotype frequencies among patients were, respectively, 68.0%, 23.2%, and 8.8%. The CC, CT, and TT genotype frequencies among controls were, respectively, 63.0%, 23.0%, and 14.0%. There was no significant difference between patients and controls (p = .480, p = .999, p = .286, respectively). At first month, respectively, through blood concentrations of MPA were significantly higher in UGT1A9 1399 C > T TT carriers than in CT and CC carriers (p = .046). The doses for these patients were lower at first month (p = .021). Acute rejection episodes were not associated with the CC vs CT or TT genotypes (p = .064).
Our results demonstrated a correlation between the UGT1A9 1399 C > T polymorphism and MPA pharmacokinetics among renal transplant patients. Determination of UGT1A9 polymorphism may help to achieve target of MPA blood concentrations.
霉酚酸在个体中的药代动力学存在差异。UGT1A9 酶是特别关注的，因为它是 MPA 葡萄糖醛酸化的主要酶。UGT1A9 基因的单核苷酸多态性可能导致 MPA 药代动力学的个体差异。本研究旨在解释土耳其肾移植患者 UGT1A9 1399C > T 多态性中 MPA 的药代动力学。
125 名活体供体移植受者和 100 名健康对照者接受聚合酶链反应-限制性片段长度多态性检测 UGT1A9 1399C > T 基因分型。采用克隆酶供体免疫测定法（CEDIA）测定 MPA 浓度。此外，在研究期间，所有患者均监测急性排斥反应和移植物功能。
患者中 UGT1A9 1399C > T CC、CT 和 TT 基因型频率分别为 68.0%、23.2%和 8.8%。对照组中 CC、CT 和 TT 基因型频率分别为 63.0%、23.0%和 14.0%。患者与对照组之间无显著性差异（p =.480、p =.999、p =.286）。在第一个月，UGT1A9 1399C > T TT 携带者的 MPA 血药浓度明显高于 CT 和 CC 携带者（p =.046）。这些患者的剂量在第一个月较低（p =.021）。急性排斥反应与 CC 与 CT 或 TT 基因型无关（p =.064）。
我们的研究结果表明，肾移植患者中 UGT1A9 1399C > T 多态性与 MPA 药代动力学相关。UGT1A9 多态性的测定可能有助于达到 MPA 血药浓度的目标。
