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

Clinical Chemistry and Laboratory Medicine : CCLM
Beatriz TaviraEliecer Coto

Abstract

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. 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. 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. 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.

References

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Aug 15, 2006·Pharmacogenetics and Genomics·Jean Nicholas RoyMichel Roger
Oct 20, 2006·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·V HaufroidM Mourad
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Apr 16, 2010·Clinical Pharmacology and Therapeutics·E ThervetC Legendre
Apr 13, 2011·Clinical Chemistry and Laboratory Medicine : CCLM·Beatriz TaviraUNKNOWN REDINREN Pharmacogenetics group
Jun 20, 2013·Pharmacogenetics and Genomics·Beatriz TaviraFrancisco Ortega
Oct 25, 2014·Circulation Journal : Official Journal of the Japanese Circulation Society·Juan GómezEliecer Coto

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Citations

Jun 18, 2016·Clinical Transplantation·Kimberly M DeiningerChristina L Aquilante
Jan 3, 2018·Critical Reviews in Microbiology·Yuehua Gong, Yuan Yuan

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