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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 and Eliecer Coto EMAIL logo
Published/Copyright: March 9, 2015
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Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 53 Issue 10

Abstract

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.

Keywords: ABCB1; P-glicoprotein; pharmacogenetics; renal transplantation; tacrolimus
Corresponding author: Eliecer Coto, PhD, Molecular Genetics, Laboratory of Medicine, Hospital Universitario Central Asturias-HUCA, 33006 Oviedo, Spain, Phone/Fax: +34 985107968, E-mail: ; Red Investigación Renal-REDINREN, Madrid, Spain; and Fundación Renal I, Alvarez de Toledo, Madrid, Spain
aBeatriz Tavira and Juan Gómez contributed equally to this work.

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Supplemental Material:

The online version of this article (DOI: 10.1515/cclm-2014-1195) offers supplementary material, available to authorized users.

Received: 2014-12-4
Accepted: 2015-1-20
Published Online: 2015-3-9
Published in Print: 2015-9-1

©2015 by De Gruyter

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https://doi.org/10.1515/cclm-2014-1195
Keywords for this article
ABCB1; P-glicoprotein; pharmacogenetics; renal transplantation; tacrolimus

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. New endocrine biomarkers and cardiovascular disease: is it time for routinely screening?
  4. Reviews
  5. Quantitative detection of amyloid-β peptides by mass spectrometry: state of the art and clinical applications
  6. Recent advances in biomarkers for Parkinson’s disease focusing on biochemicals, omics and neuroimaging
  7. Mini Review
  8. Serum calcitonin negative medullary thyroid carcinoma: a systematic review of the literature
  9. Genetics and Molecular Diagnostics
  10. ABCB1 (MDR-1) pharmacogenetics of tacrolimus in renal transplanted patients: a Next Generation Sequencing approach
  11. Novel association of FCGR2A polymorphism with age-related macular degeneration (AMD) and development of a novel CFH real-time genotyping method
  12. General Clinical Chemistry and Laboratory Medicine
  13. Assessing quality on the Sigma scale from proficiency testing and external quality assessment surveys
  14. Combining antibody tests and taking into account antibody levels improves serologic diagnosis of celiac disease
  15. Application of a point of care creatinine device for trend monitoring in kidney transplant patients: fit for purpose?
  16. LC-MS/MS method for hepcidin-25 measurement in human and mouse serum: clinical and research implications in iron disorders
  17. The relationship of fibroblast growth factors 21 and 23 and α-Klotho with platelet activity measured by platelet volume indices
  18. Neurofilament medium polypeptide (NFM) protein concentration is increased in CSF and serum samples from patients with brain injury
  19. Methods to identify saline-contaminated electrolyte profiles
  20. An international study of how laboratories handle and evaluate patient samples after detecting an unexpected APTT prolongation
  21. The influence of excipients commonly used in freeze drying on whole blood coagulation dynamics assessed by rotational thromboelastometry
  22. Reference Values and Biological Variations
  23. Biological variation of plasma osmolality obtained with capillary versus venous blood
  24. Mining of hospital laboratory information systems: a model study defining age- and gender-specific reference intervals and trajectories for plasma creatinine in a pediatric population
  25. Cancer Diagnostics
  26. Fascin is a circulating tumor marker for head and neck cancer as determined by a proteomic analysis of interstitial fluid from the tumor microenvironment
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  28. First trimester concentrations of the TTR-RBP4-retinol complex components as early markers of insulin-treated gestational diabetes mellitus
  29. Corrigendum
  30. Corrigendum to: Performance criteria and quality indicators for the pre-analytical phase
  31. Letters to the Editors
  32. Pediatric reference intervals for calculated free testosterone, bioavailable testosterone and free androgen index in the CALIPER cohort
  33. Two novel genomic rearrangements identified in suicide subjects using a-CGH array
  34. Association between physical fitness and mean platelet volume in professional soccer players
  35. Laboratory biomarkers and frailty: presentation of the FRAILOMIC initiative
  36. Spuriously high platelet counts by various automated hematology analyzers in a patient with disseminated intravascular coagulation
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