1. Influence of ABCC2, CYP2C8, and CYP2J2 Polymorphisms on Tacrolimus and Mycophenolate Sodium-Based Treatment in Brazilian Kidney Transplant Recipients.
- Author
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Genvigir FDV, Nishikawa AM, Felipe CR, Tedesco-Silva H Jr, Oliveira N, Salazar ABC, Medina-Pestana JO, Doi SQ, Hirata MH, and Hirata RDC
- Subjects
- Adult, Brazil epidemiology, Cytochrome P-450 CYP2J2, Female, Graft Rejection epidemiology, Graft Rejection prevention & control, Humans, Immunosuppressive Agents blood, Immunosuppressive Agents therapeutic use, Male, Multidrug Resistance-Associated Protein 2, Mycophenolic Acid blood, Polymorphism, Single Nucleotide, Prospective Studies, Tacrolimus blood, Treatment Outcome, Cytochrome P-450 CYP2C8 genetics, Cytochrome P-450 Enzyme System genetics, Graft Rejection genetics, Kidney Transplantation adverse effects, Multidrug Resistance-Associated Proteins genetics, Mycophenolic Acid therapeutic use, Tacrolimus therapeutic use
- Abstract
Study Objective: To investigate the influence of single nucleotide polymorphisms (SNPs) in genes encoding metabolizing enzymes (CYP2C8, CYP2J2, and UGT2B7) and transporters (ABCC2 and ABCG2) on dose and dose-adjusted trough blood concentrations (C:D ratio), clinical outcomes, and occurrence of adverse events of tacrolimus and mycophenolate sodium in Brazilian kidney transplant recipients., Design: Pharmacogenetic analysis of patients enrolled in a previously published study., Patients: One hundred forty-eight adult kidney transplant recipients treated with tacrolimus, enteric-coated mycophenolate sodium, and prednisone for 90 days posttransplantation., Measurements and Main Results: ABCC2 c.-24C>T and c.3972C>T, ABCG2 c.421C>A, CYP2C8*3, CYP2J2 c.-76G>T, and UGT2B7 c.372A>G SNPs were determined by real-time polymerase chain reaction. The CYP3A5*3C SNP data were used to eliminate the confounding effect of this variant on the results. ABCC2 c.3972T allele carriers showed higher tacrolimus C:D values than did carriers of the c.3972CC genotype. The CYP2C8*3 variant was also associated with slightly higher tacrolimus C:D values and higher estimated glomerular filtration rate but only in CYP3A5-nonexpressing patients (CYP3A5*3C/*3C carriers). None of the SNPs were associated with mycophenolate sodium dose or episodes of biopsy-confirmed acute rejection or delayed graft function. The CYP2J2 c.-76T allele was associated with increased risk for treatment-induced nausea and/or vomiting (OR: 5.30, 95% confidence interval 1.49-18.79, p<0.05)., Conclusion: The ABCC2 c.3972C >T polymorphism affected tacrolimus C:D in Brazilian kidney transplant recipients. Further, CYP2C8*3 and CYP2J2 c.-76G>T SNPs influenced the renal function of these patients and the occurrence of adverse events during treatment with tacrolimus and mycophenolate sodium., (© 2017 Pharmacotherapy Publications, Inc.)
- Published
- 2017
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