Influence of the CYP3A4/5 genetic score and ABCB1 polymorphisms on tacrolimus exposure and renal function in Brazilian kidney transplant patients

Página do item simplificado
dc.citation.issue10
dc.citation.volume26
dc.contributor.authorGenvigir, Fabiana D. V.
dc.contributor.authorSalgado, Patricia C.
dc.contributor.authorFelipe, Claudia Rosso [UNIFESP]
dc.contributor.authorLuo, Elena Y. F.
dc.contributor.authorAlves, Camila
dc.contributor.authorCerda, Alvaro
dc.contributor.authorTedesco-Silva Junior, Hélio [UNIFESP]
dc.contributor.authorPestana, Jose Osmar Medina [UNIFESP]
dc.contributor.authorOliveira, Nagilla Ione de [UNIFESP]
dc.contributor.authorRodrigues, Alice C.
dc.contributor.authorDoi, Sonia Q.
dc.contributor.authorHirata, Mario H.
dc.contributor.authorHirata, Rosario D. C.
dc.coveragePhiladelphia
dc.date.accessioned2020-07-31T12:47:42Z
dc.date.available2020-07-31T12:47:42Z
dc.date.issued2016
dc.description.abstractBackgroundPolymorphisms in genes encoding transport proteins and metabolizing enzymes involved in tacrolimus (TAC) disposition may be important sources of individual variability during treatment.ObjectiveThe aim of this study was to investigate the effect of combined CYP3A4 and CYP3A5 variants, using a CYP3A4/5 genetic score, and ABCB1 polymorphisms on therapeutic TAC monitoring and their relationship with clinical outcomes.Material and methodsBrazilian kidney transplant recipients (n=151), who received TAC over 3 months after transplantation, were genotyped for CYP3A4 rs2242480 (g.20230G>A), CYP3A5 rs15524 (g.31611C>T) and rs776746 (g.6986A>G), ABCB1 rs1128503 (c.1236C>T), rs1045642 (c.3435C>T), and rs2032582 (c.2677G>T/A) polymorphisms.ResultsFrequencies of CYP3A4 g.20230A, CYP3A5 g.31611C, and g.6986A were 0.37, 0.26, and 0.28, respectively. These alleles were associated with TAC rapid metabolization and were used for CYP3A4/5 genetic score construction. A higher CYP3A4/5 genetic score was associated with higher TAC dose and lower concentrations for dose administered (Co/D, P<0.05). Ninety days after transplantation, the presence of two or more rapid metabolization alleles contributed toward 27.7% of Co/D variability and was associated with a lower estimated glomerular filtration rate values (P<0.05). For ABCB1, the frequencies of c.1236T, c.3435T, and c.2677T/A alleles were 0.42, 0.42, and 0.33/0.04. At 30 days after transplantation, patients carrying ABCB1 c.1236TT+c.3435TT+(c.2677TT+TA) genotypes had higher TAC Co/D than those with common or heterozygous genotypes (P<0.05).ConclusionThe results show the impact of the CYP3A4/5 genetic score on TAC exposure and renal function in Brazilian patients. Furthermore, ABCB1 polymorphisms, in a combined analysis, influenced TAC Co/D at 30 days after transplantation.en
dc.description.affiliationUniv Sao Paulo, Sch Pharmaceut Sci, Dept Clin & Toxicol Anal, Sao Paulo, Brazil
dc.description.affiliationUniv Sao Paulo, Inst Biomed Sci, Dept Pharmacol, Sao Paulo, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Hosp Rim, Nephrol Div, Sao Paulo, Brazil
dc.description.affiliationUniv La Frontera, Ctr Mol Biol & Pharmacogenet, BIOREN CEGIN, Temuco, Chile
dc.description.affiliationUniformed Serv Univ Hlth Sci, Sch Med, Bethesda, MD USA
dc.description.affiliationUnifespNephrology Division, Hospital do Rim, Universidade Federal de São Paulo, Sao Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipIDFAPESP: 2011/10039-6
dc.format.extent462-472
dc.identifierhttp://dx.doi.org/10.1097/FPC.0000000000000237
dc.identifier.citationPharmacogenetics And Genomics. Philadelphia, v. 26, n. 10, p. 462-472, 2016.
dc.identifier.doi10.1097/FPC.0000000000000237
dc.identifier.issn1744-6872
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/57026
dc.identifier.wosWOS:000384519700003
dc.language.isoeng
dc.publisherLippincott Williams & Wilkins
dc.relation.ispartofPharmacogenetics And Genomics
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.subjectABCB1en
dc.subjectCYP3A4en
dc.subjectCYP3A5en
dc.subjectgenetic scoreen
dc.subjectpolymorphismen
dc.subjectrenal transplantationen
dc.subjecttacrolimusen
dc.titleInfluence of the CYP3A4/5 genetic score and ABCB1 polymorphisms on tacrolimus exposure and renal function in Brazilian kidney transplant patientsen
dc.typeinfo:eu-repo/semantics/article
Arquivos
Coleções
EPM - Artigos