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1.
Pharmacotherapy ; 37(5): 535-545, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28316087

RESUMO

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.


Assuntos
Citocromo P-450 CYP2C8/genética , Sistema Enzimático do Citocromo P-450/genética , Rejeição de Enxerto/genética , Transplante de Rim , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Ácido Micofenólico/uso terapêutico , Tacrolimo/uso terapêutico , Adulto , Brasil/epidemiologia , Citocromo P-450 CYP2J2 , Feminino , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/prevenção & controle , Humanos , Imunossupressores/sangue , Imunossupressores/uso terapêutico , Transplante de Rim/efeitos adversos , Masculino , Proteína 2 Associada à Farmacorresistência Múltipla , Ácido Micofenólico/sangue , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos , Tacrolimo/sangue , Resultado do Tratamento
2.
Pharmacotherapy ; 37(5): 535-545, 2017.
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: biblio-1065489

RESUMO

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)...


Assuntos
Cristalização , Polimorfismo Genético , Tacrolimo , Transplante de Rim
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