Abstract
Background
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 PPP3CA c.249G>A variant on the clinical outcomes of kidney transplant recipients.
Patients and methods
A total of 148 Brazilian patients received tacrolimus (TAC)-based immunosuppressive therapy for 90 days post-kidney transplantation. The PPP3CA rs3730251 (c.249G>A) polymorphism was determined by real-time polymerase chain reaction. Single-nucleotide polymorphism (SNP) data for CYP3A5 rs776746 (CYP3A5*3C; g.6986A>G) were used to eliminate the confounding effects of this variant.
Results
The PPP3CA 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, PPP3CA 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 CYP3A5*3C SNP status (p=0.086).
Conclusion
The PPP3CA c.249G>A variant does not influence the clinical outcomes of Brazilian patients in the early phase of TAC-based immunosuppressive regimen.
Acknowledgments
The authors thank Cristina M Fajardo, Vivian Bonezi, Antony BC Salazar, and Nagilla I Oliveira for technical support and assistance with patient enrollment. This work was supported by grants from FAPESP (project # 2011/10039-6).
Disclosure
Fabiana DV Genvigir is a recipient of a fellowship (#2014/18871-0) from FAPESP, Sao Paulo, Brazil. Mario H Hirata and Rosario DC Hirata are recipients of fellowships from CNPq, Brasilia, Brazil. The other authors report no conflicts of interest in this work.