Influence of ABCC2, CYP2C8, and CYP2J2 Polymorphisms on Tacrolimus and Mycophenolate Sodium-Based Treatment in Brazilian Kidney Transplant Recipients

Influence of ABCC2, CYP2C8, and CYP2J2 Polymorphisms on Tacrolimus and Mycophenolate Sodium-Based Treatment in Brazilian Kidney Transplant Recipients

Author Genvigir, Fabiana D. V. Google Scholar
Nishikawa, Alvaro M. Google Scholar
Felipe, Claudia R. Autor UNIFESP Google Scholar
Tedesco-Silva, Helio, Jr. Autor UNIFESP Google Scholar
Oliveira, Nagilla Autor UNIFESP Google Scholar
Salazar, Antony B. C. Google Scholar
Medina-Pestana, Jose O. Autor UNIFESP Google Scholar
Doi, Sonia Q. Google Scholar
Hirata, Mario H. Google Scholar
Hirata, Rosario D. C. Google Scholar
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.
Keywords ABCC2
ABCG2
CYP2C8
CYP2J2
kidney transplantation
mycophenolate sodium
polymorphism
tacrolimus
UGT2B7
xmlui.dri2xhtml.METS-1.0.item-coverage Hoboken
Language English
Sponsor Sao Paulo Research Foundation (FAPESP)
FAPESP, Sao Paulo, Brazil
National Council for Scientific and Technological Development (CNPq), Brasilia, Brazil
Grant number FAPESP: 2011/10039-6
FAPESP: 2016/13118-8
Date 2017
Published in Pharmacotherapy. Hoboken, v. 37, n. 5, p. 535-545, 2017.
ISSN 0277-0008 (Sherpa/Romeo, impact factor)
Publisher Wiley
Extent 535-545
Origin http://dx.doi.org/10.1002/phar.1928
Access rights Closed access
Type Article
Web of Science ID WOS:000403670100005
URI https://repositorio.unifesp.br/handle/11600/54553

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