ABCB1 (MDR-1) pharmacogenetics of tacrolimus in renal transplanted patients: A Next Generation Sequencing approach

Beatriz Tavira, Juan Gómez, Carmen Diaz-Corte, Beatriz Suarez, Diego Coronel, Manuel Arias, Carlos López-Larrea, Sara Iglesias, Belén Alonso, Emilio Rodrigo, Eliecer Coto

Producción científica: Contribución a una revistaArtículorevisión exhaustiva

3 Citas (Scopus)


Background: A CYP3A5 gene polymorphism is the main determinant of Tacrolimus (Tac) dose requirements among renal transplanted patients. In spite of the utility of CYP3A5 genotyping to predict the Tac-dose, many patients exhibit an out of range blood Tac level and it is thus likely that other genes/polymorphisms contribute to define Tac bioavailability. To address this issue we searched for coding sequence variants in the ABCB1/MDR1 gene in renal transplanted patients treated with Tac and who had out of the range blood levels. Methods: We studied 100 renal transplanted patients treated with Tac, 60 of whom had Tac blood levels below (n=39) and above (n=21) the target range (10-15 ng/mL) at 1 week post-transplant. The DNA was subjected to multiplex amplification followed by massive parallel semiconductor sequencing in the Ion Torrent personal genome machine. Results: We found four missense changes, all reported and present in cases above and below the blood Tac target. In addition, we did not find differences in the allele and genotype frequencies for the common rs1045642 polymorphism (p.I1145I) between the groups. Conclusions: Our results suggested that the ABCB1 variants had no effect on the risk of showing out of range Tac blood levels among renal transplanted patients.

Idioma originalInglés
Páginas (desde-hasta)1515-1519
Número de páginas5
PublicaciónClinical Chemistry and Laboratory Medicine
EstadoPublicada - 1 sep. 2015
Publicado de forma externa


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