薬理ゲノミクスと薬理プロテオミクスのジャーナル

概要

Influence of SLCO1B1 and SLCO2B1 Polymorphisms on Tacrolimus Pharmacokinetics and Clinical Response

Camila Alves, Claudia R Felipe, Alvaro M Nishikawa, Patricia C Salgado, Cristina Fajardo, Helio T Silva Jr, Jose Osmar M Pestana, Denize Zetchaku, Glaucio Spinelli, Nagilla Oliveira, Mario Hiroyuki Hirata, Rosario DC Hirata and Alice C Rodrigues

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.