Influence of SLCO1B1 and SLCO2B1 Polymorphisms on Tacrolimus Pharmacokinetics and Clinical ResponseCamila Alves1, Claudia R Felipe2, Alvaro M Nishikawa1, Patricia C Salgado1, Cristina Fajardo1, Helio T Silva Jr2, Jose Osmar M Pestana2, Denize Zetchaku2, Glaucio Spinelli2, Nagilla Oliveira2, Mario Hiroyuki Hirata1, Rosario DC Hirata1 and Alice C Rodrigues3*
- *Corresponding Author:
- Alice Cristina Rodrigues, PhD
Institute of Biomedical Sciences
Department of Pharmacology, University of Sao Paulo
Av. Prof. Lineu Prestes, 1524, 1°andar
sala 206, 05508-000, Sao Paulo, SP, Brazil
E-mail: [email protected]
Received date: May 28, 2014; Accepted date: May 29, 2014; Published date: June 06, 2014
Citation: Alves C, Felipe CR, Nishikawa AM, Salgado PC, Fajardo C, et al. (2014) Influence of SLCO1B1 and SLCO2B1 Polymorphisms on Tacrolimus Pharmacokinetics and Clinical Response. J Pharmacogenomics Pharmacoproteomics 5:134. doi: 10.4172/2153-0645.1000134
Copyright: © 2014 Alves C, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Background: Immunosuppressant such as tacrolimus have narrow therapeutic range and are often associated with increased risk of nefrotoxicity in individuals that receive this drug after renal transplantation. Variants in transporters genes have been associated with variability in plasma concentration of tacrolimus and higher risk of adverse effects. Our aim was to investigate the effect of SLCO1B1 (c.388A>G, c.521T>C) and SLCO2B1 (c.- 71T>C) variants on the efficacy and safety of tacrolimus immunosuppressive therapy in kidney transplant recipients.
Methods: SLCO1B1 and SLCO2B1 polymorphisms were detected by TaqMan genotyping and were associated to tacrolimus pharmacokinetics and incidence of acute rejection or diarrhea.
Results: Carriers of the allele SLCO1B1 c.388G had lower dose adjusted blood concentration (CO/D) of tacrolimus when compared to 388AA carriers, while SLCO1B1 c.521T>C had no effect. Carriers of CC genotype of SLCO2B1 c.-71T>C SNP had higher CO/D of tacrolimus when compared to TT carriers. When we consider the effect of the haplotype (c.388A>G and c.521T>C) of SLCO1B1 on tacrolimus CO/D and incidence of rejection, carriers of SLCO1B1 *1b haplotype had lower CO/D and lower incidence of rejection when compared to wild type haplotype *1a (p>0.05).
Conclusions: SLCO1B1 and SLCO2B1 polymorphisms can contribute for a more safety immunossupressive treatment in kidney recipients.