ATC Abstracts

American Transplant Congress abstracts

  • Home
  • Meetings Archive
    • 2020 American Transplant Congress
    • 2019 American Transplant Congress
    • 2018 American Transplant Congress
    • 2017 American Transplant Congress
    • 2016 American Transplant Congress
    • 2015 American Transplant Congress
    • 2013 American Transplant Congress
  • Keyword Index
  • Resources
    • 2016 Resources
      • 2016 Welcome Letter
      • ATC 2016 Program Planning Committees
      • ASTS Council 2015-2016
      • AST Board of Directors 2015-2016
    • 2015 Resources
      • 2015 Welcome Letter
      • ATC 2015 Program Planning Committees
      • ASTS Council 2014-2015
      • AST Board of Directors 2014-2015
      • 2015 Conference Schedule
  • Advanced Search

Variants Associated With Tacrolimus Troughs in European American Kidney Transplant Recipients: A Genome Wide Association Study

P. Jacobson,1 M. Miller,2 D. Schladt,3 A. Israni,3 K. Sanghavi,1 C. Dorr,3 R. Remmel,1 W. Guan,4 A. Matas,5 W. Oetting.1

1College of Pharmacy, University of MN, Minneapolis, MN
2Department of Psychology, University of MN, Minneapolis, MN
3Department of Nephrology and Chronic Disease Research Group, Minneapolis Medical Research Foundation, Hennepin County Medical Center, Minneapolis, MN
4Department of Biostatistics, University of MN, Minneapolis, MN
5Department of Surgery, University of MN, Minneapolis, MN.

Meeting: 2015 American Transplant Congress

Abstract number: B257

Keywords: Calcineurin, Gene polymorphism, Immunosuppression, Monitoring

Session Information

Date: Sunday, May 3, 2015

Session Name: Poster Session B: Translational Genetics and Proteomics in Transplantation

Session Time: 5:30pm-6:30pm

 Presentation Time: 5:30pm-6:30pm

Location: Exhibit Hall E

Related Abstracts
  • Development and Validation of a Genotype Guided Tacrolimus Dosing Equation for African American (AA) Kidney Transplant Recipients
  • Single Nucleotide Polymorphisms (SNPs) Associated With Acute Rejection in European American Kidney Transplant Recipients: A Genome Wide Association Study (GWAS)

Tacrolimus (tac) is dependent on CYP3A4/5 for metabolism. Variability in the metabolism is influenced by CYP3A5*3 alleles. This variant and clinical factors explain around 50% of variability in tac troughs. Other variants may be present that explain additional variability. The purpose of this study is to identify new variants which are determinants of tac troughs in a large, European ancestry cohort of (n=1457) adult kidney or kidney pancreas transplant recipients in a 7-center consortium. European kidney transplant recipients enrolled in the DeKAF Genomics study and received tac were genotyped using an exome-plus Affymetrix TXArray chip containing 450,130 markers after QC. The associations between variants across the genome and dose normalized whole blood tac troughs (n=25481) in the first 6 mo posttx were evaluated using repeated measures regression analysis.

The median (range) recipient age was 52.6 yrs (18-83), 63% were males and 66% received a living donor transplant. Median (range) tac troughs and dose were 8.4 ng/mL (0.3-75.9) and 5.5 mg/day (0.1-36), respectively. Seven variants (rs35599367, rs74516408, rs7792939, rs62471929, rs4986910, rs62471957, rs62474460) were associated with tac troughs after adjusting for CYP3A5*3 and four ancestry principal components (all genome wide significant, p<10-8). The analysis was then adjusted for the top SNP, rs35599367 (CYP3A4*22) and no variants remained significant at the genome wide level (p>10-7), although, rs4986910 (CYP3A4*3) continued to be important with p=0.001. Each CYP3A5*3 allele increased the dose-normalized tac trough by 84% and each CYP3A4*22 by 37% and CYP3A4*3 by 41%. Allele frequencies for CYP3A5*3, CYP3A4*22 and CYP3A4*3 were 0.93, 0.057 and was 0.011, respectively. CYP3A5*3, CYP3A4*22 and CYP3A4*3 were associated with tac troughs in our cohort of European Americans. Future studies identifying less frequent variants which may have important effects on troughs are warranted. This project was supported by NIAID.

  • Tweet
  • Email
  • Print

To cite this abstract in AMA style:

Jacobson P, Miller M, Schladt D, Israni A, Sanghavi K, Dorr C, Remmel R, Guan W, Matas A, Oetting W. Variants Associated With Tacrolimus Troughs in European American Kidney Transplant Recipients: A Genome Wide Association Study [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/variants-associated-with-tacrolimus-troughs-in-european-american-kidney-transplant-recipients-a-genome-wide-association-study/. Accessed April 18, 2021.

« Back to 2015 American Transplant Congress

Most Viewed Abstracts

  • This Week
  • This Month
  • All Time
  • Subtherapeutic Low Tacrolimus Trough Levels (≤3.5 Ng /ml) Are A Risk Factor For Acute Rejection And Creatinine Doubling.
  • Low GFR after Kidney Donation Is Not Chronic Kidney Disease
  • Is There a Difference Between DCD and DBD Kidney Transplantation with Similar KDPI?
  • Penis Transplantation: First U.S. Experience.
  • Kidney Dialysis after Heart Transplantation: The Short and Long Term Outcomes
  • Subtherapeutic Low Tacrolimus Trough Levels (≤3.5 Ng /ml) Are A Risk Factor For Acute Rejection And Creatinine Doubling.
  • Low GFR after Kidney Donation Is Not Chronic Kidney Disease
  • Is There a Difference Between DCD and DBD Kidney Transplantation with Similar KDPI?
  • Penis Transplantation: First U.S. Experience.
  • Live Related Kidney Transplant Experience in Abuja, Nigeria – First Eight Cases Ever.
  • Penis Transplantation: First U.S. Experience.
  • Is There a Difference Between DCD and DBD Kidney Transplantation with Similar KDPI?
  • Low GFR after Kidney Donation Is Not Chronic Kidney Disease
  • Evidence of a Clinically Significant Drug-Drug Interaction between Cannabidiol and Tacrolimus: A Case Report
  • Kidney Dialysis after Heart Transplantation: The Short and Long Term Outcomes

Visit Our Partner Sites

American Transplant Congress (ATC)

Visit the official site for the American Transplant Congress »

American Journal of Transplantation

The official publication for the American Society of Transplantation (AST) and the American Society of Transplant Surgeons (ASTS) »

American Society of Transplantation (AST)

An organization of more than 3000 professionals dedicated to advancing the field of transplantation. »

American Society of Transplant Surgeons (ASTS)

The society represents approximately 1,800 professionals dedicated to excellence in transplantation surgery. »

Copyright © 2013-2021 by American Society of Transplantation and the American Society of Transplant Surgeons. All rights reserved.

Privacy Policy | Terms of Use

loading Cancel
Post was not sent - check your email addresses!
Email check failed, please try again
Sorry, your blog cannot share posts by email.
This site uses cookies: Find out more.