Influence of SLCO1B1 and SLCO2B1 Polymorphisms on Tacrolimus Pharmacokinetics and Clinical Efficacy and Safety
Hospital do Rim e Hipertensão, São Paulo, Brazil
Faculdade de Ciencias Farmaceuticas USP, São Paulo, Brazil
Meeting: 2013 American Transplant Congress
Abstract number: D1600
Introduction: Tacrolimus (TAC) has a narrow therapeutic range and is associated with increased risk of nefrotoxicity after kidney transplantation. Variants in transporter genes have been associated with variability in TAC blood concentrations of and higher risk of adverse effects. Our aim was to investigate the effect of genetic variants of SLCO1B1 (c.388A>G, c.521T>C) and SLCO2B1 (c.-71T>C) genes on the efficacy and safety of TAC immunosuppressive therapy in kidney transplant recipients. Methods: We evaluated 129 renal transplant recipients who received TAC, mycophenolate and prednisone. SLCO1B1 rs2306283 (c.388A>G) and rs4149056 (c.521T>C), and SLCO2B1 rs2851069 (c.-71T>C) polymorphisms were detected by TaqMan genotyping and were associated to TAC concentrations and incidence of acute rejection or diarrhea. Results: The mean age was 43±16 year, 46.5% Caucasian, 70.5% male and 41.3% recipients of deceased donor kidney. The frequencies of the two variants (c.388A>G and c.521T>C) for SLCO1B1 gene was 53% and 14%, respectively. Minor allele frequency (MAF) for SLCO2B1-71C allele was 46%. Haplotypes for SLCO1B1 were defined based on the presence of c.388A>G and c.521T>C SNPs polymorphisms alone or in combination, as follows: SLCO1B1 *1a (wild type), *1b (c.388G), *5 (c.521C) or *15 (c.388G and c.521C). The frequencies of the alleles were *1a (43.2%); *1b (40.9%); *15 (14.7%) and *5 (1.2%). Carriers of the variant allele SLCO1B1 c.388G (*1b) had lower dose adjusted tacrolimus blood concentration compared to wild-type allele (*1a) or *5+*15 haplotypes (1.093±0.13 vs. 2.055±0.09 vs. 1.729±0.1280 ng.mL-1/mg). The incidence of acute rejection was lower in carriers of *1b haplotype (34.3%) when compared to haplotype *1a (48.5%) (p=0.017). Diarrhea occurred in 27% of the patients but was not associated with genotype or alleles of SLCO2B1 or SLCO1B1 SNPs (p>0.05). Conclusion: SLCO2B1 or SLCO1B1 SNPs partially contribute to the variability observed in tacrolimus blood concentration and its efficacy for the prevention of acute rejection.
To cite this abstract in AMA style:
Alves C, Felipe C, Nishikawa A, Salgado P, Fajardo C, Spinelli G, Tedesco H, Pestana JMedina-, Hirata M, Hirata R, Rodrigues A. Influence of SLCO1B1 and SLCO2B1 Polymorphisms on Tacrolimus Pharmacokinetics and Clinical Efficacy and Safety [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/influence-of-slco1b1-and-slco2b1-polymorphisms-on-tacrolimus-pharmacokinetics-and-clinical-efficacy-and-safety/. Accessed May 14, 2025.« Back to 2013 American Transplant Congress