CYP3A5 and PPARA genetic variants are associated with low trough concentration to dose ratio of tacrolimus in kidney transplant recipients.

Autor: Everton JBF; Laboratory of Genomic and Histocompatibility Studies, University Hospital of the Federal University of Maranhão, São Luís, Brazil.; Postgraduate Program in Adult Health (PPGSAD), Federal University of Maranhão, São Luís, Brazil., Patrício FJB; Laboratory of Genomic and Histocompatibility Studies, University Hospital of the Federal University of Maranhão, São Luís, Brazil., Faria MS; Postgraduate Program in Adult Health (PPGSAD), Federal University of Maranhão, São Luís, Brazil.; Clinical Research Center, University Hospital of the Federal University of Maranhão, São Luís, Brazil., Ferreira TCA; Kidney Transplant Unit, University Hospital of the Federal University of Maranhão, São Luís, Brazil., Romao EA; Department of Internal Medicine, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil., Silva GEB; Postgraduate Program in Adult Health (PPGSAD), Federal University of Maranhão, São Luís, Brazil.; Pathology Unit, University Hospital of the Federal University of Maranhão, São Luís, Brazil., Magalhães M; Laboratory of Genomic and Histocompatibility Studies, University Hospital of the Federal University of Maranhão, São Luís, Brazil. magalhaes_ms@yahoo.com.br.; Postgraduate Program in Adult Health (PPGSAD), Federal University of Maranhão, São Luís, Brazil. magalhaes_ms@yahoo.com.br.; Clinical Research Center, University Hospital of the Federal University of Maranhão, São Luís, Brazil. magalhaes_ms@yahoo.com.br.
Jazyk: angličtina
Zdroj: European journal of clinical pharmacology [Eur J Clin Pharmacol] 2021 Jun; Vol. 77 (6), pp. 879-886. Date of Electronic Publication: 2021 Jan 05.
DOI: 10.1007/s00228-020-03076-8
Abstrakt: Purpose: Genetic polymorphisms have been associated with variation in the metabolism of tacrolimus (TAC) in kidney transplant patients. This study is aimed at assessing the impact of allelic variants of CYP3A5 and PPARA genes on the pharmacokinetics (PK) of TAC in Brazilian kidney transplant recipients in the first-year post-transplant.
Methods: A total of 127 patients were included for genetic evaluation. Genomic DNA was isolated from peripheral blood and real-time PCR was used to analyze the main polymorphisms described for the genes CYP3A5 (rs776746; C > G) and PPARA (rs4823613; A > G and rs4253728; G > A).
Results: CYP3A5 expressors showed a lower Co/dose ratio than non-expressors, with the median values of this parameter <1.01 ng/mL/mg in the first group at all evaluated times. Additionally, PPARA variant homozygotes had a lower Co/D ratio than wild allele carriers in the 12-month post-transplant period, with a median value of 0.65 ng/mL/mg. In the CYP3A5 expressers, the presence of the variant homozygous genotype PPARA was associated with a lower value of Co/D compared with the other genotypic groups at month 12.
Conclusion: In the population under study, polymorphisms on CYP3A5 and PPARA were identified as determining and independent factors associated with the reduction of Co/D of TAC. Thus, the genotyping of these genetic variants may be a useful tool for the individualized prescription of TAC in kidney transplant patients.
Databáze: MEDLINE
Externí odkaz: