Influence of ABCC2, CYP2C8, and CYP2J2 Polymorphisms on Tacrolimus and Mycophenolate Sodium-Based Treatment in Brazilian Kidney Transplant Recipients.
Pharmacotherapy
; 37(5): 535-545, 2017 May.
Article
en En
| MEDLINE
| ID: mdl-28316087
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 (CD 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 MAINRESULTS:
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 CD values than did carriers of the c.3972CC genotype. The CYP2C8*3 variant was also associated with slightly higher tacrolimus CD 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 CD 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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Trasplante de Riñón
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Tacrolimus
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Sistema Enzimático del Citocromo P-450
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Proteínas Asociadas a Resistencia a Múltiples Medicamentos
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Citocromo P-450 CYP2C8
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Rechazo de Injerto
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Ácido Micofenólico
Tipo de estudio:
Observational_studies
/
Risk_factors_studies
Límite:
Adult
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Female
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Humans
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Male
País/Región como asunto:
America do sul
/
Brasil
Idioma:
En
Revista:
Pharmacotherapy
Año:
2017
Tipo del documento:
Article
País de afiliación:
Brasil