Salgado Patricia C, Genvigir Fabiana Dv, Felipe Claudia R, Tedesco-Silva Helio, Medina-Pestana Jose O, Doi Sonia Q, Hirata Mario H, Hirata Rosario Dc
Department of Clinical and Toxicological Analysis, School of Pharmaceutical Sciences, University of Sao Paulo.
Division of Nephrology, Hospital do Rim, Federal University of Sao Paulo, Sao Paulo, Brazil.
Pharmgenomics Pers Med. 2017 Mar 31;10:101-106. doi: 10.2147/PGPM.S131390. eCollection 2017.
The effects of genetic variants related to the pharmacodynamic mechanisms of immunosuppressive drugs on their therapeutic efficacy and safety have been poorly explored. This study was performed to investigate the influence of the c.249G>A variant on the clinical outcomes of kidney transplant recipients.
A total of 148 Brazilian patients received tacrolimus (TAC)-based immunosuppressive therapy for 90 days post-kidney transplantation. The rs3730251 (c.249G>A) polymorphism was determined by real-time polymerase chain reaction. Single-nucleotide polymorphism (SNP) data for rs776746 (; g.6986A>G) were used to eliminate the confounding effects of this variant.
The c.249G>A SNP did not influence early TAC exposure, renal function, or other laboratory parameters, including levels of urea, creatinine, glucose, and lipids, and blood counts. This variant also did not account for the cumulative incidence of biopsy-confirmed acute rejection or delayed graft function. Regarding adverse events, c.249A allele carriers initially had a 3.05-fold increased probability of treatment-induced blood and lymphatic system disorders compared with c.249GG genotype individuals (95% confidence interval: 1.10-8.48, p=0.032). However, this result was not maintained after adjusting for body weight and SNP status (p=0.086).
The c.249G>A variant does not influence the clinical outcomes of Brazilian patients in the early phase of TAC-based immunosuppressive regimen.
与免疫抑制药物药效学机制相关的基因变异对其治疗效果和安全性的影响尚未得到充分研究。本研究旨在探讨c.249G>A变异对肾移植受者临床结局的影响。
共有148例巴西患者在肾移植后接受了为期90天的基于他克莫司（TAC）的免疫抑制治疗。通过实时聚合酶链反应确定rs3730251（c.249G>A）多态性。使用rs776746（; g.6986A>G）的单核苷酸多态性（SNP）数据来消除该变异的混杂效应。
c.249G>A SNP不影响早期TAC暴露、肾功能或其他实验室参数，包括尿素、肌酐、葡萄糖、脂质水平和血细胞计数。该变异也与活检证实的急性排斥反应或移植肾功能延迟的累积发生率无关。关于不良事件，与c.249GG基因型个体相比，c.249A等位基因携带者最初发生治疗引起的血液和淋巴系统疾病的概率增加3.05倍（95%置信区间：1.10-8.48，p=0.032）。然而，在调整体重和SNP状态后，这一结果未得到维持（p=0.086）。
c.249G>A变异不影响巴西患者在基于TAC免疫抑制方案早期阶段的临床结局。
