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Association of the PPP3CA c.249G>A variant with clinical outcomes of tacrolimus-based therapy in kidney transplant recipients

Overview of attention for article published in Pharmacogenomics and Personalized Medicine, March 2017
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Title
Association of the <em>PPP3CA</em> c.249G&gt;A variant with clinical outcomes of tacrolimus-based therapy in kidney transplant recipients
Published in
Pharmacogenomics and Personalized Medicine, March 2017
DOI 10.2147/pgpm.s131390
Pubmed ID
Authors

Patricia C Salgado, Fabiana DV Genvigir, Claudia R Felipe, Helio Tedesco-Silva Jr, Jose Osmar Medina-Pestana, Sonia Q Doi, Mario H Hirata, Rosario DC Hirata

Abstract

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. 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. 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). The PPP3CA c.249G>A variant does not influence the clinical outcomes of Brazilian patients in the early phase of TAC-based immunosuppressive regimen.

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Geographical breakdown

Country Count As %
Unknown 18 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 4 22%
Other 2 11%
Researcher 2 11%
Student > Ph. D. Student 2 11%
Student > Bachelor 1 6%
Other 3 17%
Unknown 4 22%
Readers by discipline Count As %
Medicine and Dentistry 3 17%
Agricultural and Biological Sciences 2 11%
Pharmacology, Toxicology and Pharmaceutical Science 2 11%
Psychology 1 6%
Unspecified 1 6%
Other 0 0%
Unknown 9 50%