ATC Abstracts

American Transplant Congress abstracts

  • Home
  • Meetings Archive
    • 2022 American Transplant Congress
    • 2021 American Transplant Congress
    • 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
    • 2021 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
  • Search

Differences in Tacrolimus Troughs and Doses Between Caucasians and African Americans with Two CYP3A5 Loss-of-Function Alleles: Looking Beyond CYP3A5 Expression.

W. Oetting,1 D. Schladt,2 W. Guan,1 R. Remmel,1 C. Dorr,2 K. Sanghavi,1 A. Matas,1 R. Mannon,3 A. Israni,2 P. Jacobson,1 For DeKAF Genomics,1 GEN-03 Investigators.1

1University of Minnesota, Minneapolis, MN
2Hennepin County Medical Center and Minneapolis Medical Research Foundation, Minneapolis, MN
3University of Alabama, Birmingham, AL.

Meeting: 2016 American Transplant Congress

Abstract number: C251

Keywords: Gene polymorphism, Genomics, Immunosuppression, Polymorphism

Session Information

Session Name: Poster Session C: Poster Session 1: Kidney Complications-Other

Session Type: Poster Session

Date: Monday, June 13, 2016

Session Time: 6:00pm-7:00pm

 Presentation Time: 6:00pm-7:00pm

Location: Halls C&D

Higher tacrolimus (TAC) dose requirements and lower TAC troughs (TT) in African Americans (AA) relative to Caucasians (CA) have been presumed to be due to a higher frequency of the CYP3A5*1 allele in AAs which results in expression of CYP3A enzyme (and more rapid TAC metabolism). We hypothesized that the CYP3A5*1 allele is not the only reason for enhanced TAC clearance observed in AA. To determine if additional genes may be associated with variation in TT, we compared CA to AA kidney transplant recipients, where all recipients of both populations carried two CYP3A5 loss-of-function alleles (*3, rs776746; *6, rs10264272; or *7, rs41303343) resulting in an absence of CYP3A5 expression. The cohort consisted of 1,430 individuals (100 AA and 1,330 CA) from five study sites. TT were clinically measured at each site. A total of 14,427 TT were analyzed (950 from AA and 13,477 from CA). We found that TT early post-transplant were approximately 1 ng/ml lower in the AA compared to CA recipients, but after day 35 post-tx TT were similar and in a multivariable model including transplant center, time from transplant and simultaneous pancreas-kidney transplant race was not significant variable (p=0.32). Total daily TAC doses were approximately 0.9 mg/day higher in AA than in CA after day 24 post-tx (p=6.6E-4). Even after normalizing for dose and weight, TT remained lower in AA (p=0.02). These data suggest that there may be additional variants in genes that result in higher tacrolimus dose requirements in AA. Potential genes that result in greater AA TAC clearance may be CYP3A4 (which is also involved in tacrolimus metabolism), genes known to influence CYP3A expression or genes which affect enzyme activity. A complete understanding of the impact of population specific genomic variants in genes responsible for TAC metabolism is important to a precision medicine approach to transplant immunosuppression. (Funded by NIAID).

CITATION INFORMATION: Oetting W, Schladt D, Guan W, Remmel R, Dorr C, Sanghavi K, Matas A, Mannon R, Israni A, Jacobson P, For DeKAF Genomics, GEN-03 Investigators Differences in Tacrolimus Troughs and Doses Between Caucasians and African Americans with Two CYP3A5 Loss-of-Function Alleles: Looking Beyond CYP3A5 Expression. Am J Transplant. 2016;16 (suppl 3).

  • Tweet
  • Click to email a link to a friend (Opens in new window) Email
  • Click to print (Opens in new window) Print

To cite this abstract in AMA style:

Oetting W, Schladt D, Guan W, Remmel R, Dorr C, Sanghavi K, Matas A, Mannon R, Israni A, Jacobson P, Genomics ForDeKAF, Investigators GEN-03. Differences in Tacrolimus Troughs and Doses Between Caucasians and African Americans with Two CYP3A5 Loss-of-Function Alleles: Looking Beyond CYP3A5 Expression. [abstract]. Am J Transplant. 2016; 16 (suppl 3). https://atcmeetingabstracts.com/abstract/differences-in-tacrolimus-troughs-and-doses-between-caucasians-and-african-americans-with-two-cyp3a5-loss-of-function-alleles-looking-beyond-cyp3a5-expression/. Accessed May 30, 2025.

« Back to 2016 American Transplant Congress

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 © 2013-2025 by American Society of Transplantation and the American Society of Transplant Surgeons. All rights reserved.

Privacy Policy | Terms of Use | Cookie Preferences