Influence of POR*28 Genotype on Tacrolimus Disposition in Heart Transplant Recipients
1University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO
2University of Colorado School of Medicine, Aurora, CO.
Meeting: 2015 American Transplant Congress
Abstract number: B261
Keywords: Genomics, Heart transplant patients, Immunosuppression, Pharmacokinetics
Session Information
Session Name: Poster Session B: Translational Genetics and Proteomics in Transplantation
Session Type: Poster Session
Date: Sunday, May 3, 2015
Session Time: 5:30pm-6:30pm
Presentation Time: 5:30pm-6:30pm
Location: Exhibit Hall E
Polymorphisms in P450 oxidoreductase (POR) have been shown to modulate CYP3A activity and alter the pharmacokinetics of CYP3A substrates, such as tacrolimus (TAC). The objective of this study was to evaluate the effect of POR*28 genotype on TAC disposition in heart transplant (HTx) recipients.
Methods: This cross-sectional study included HTx patients who were greater than 1-year post-Tx and receiving TAC. TAC trough levels and doses were abstracted from medical records. Patients were genotyped for the POR*28 and CYP3A5*3 polymorphisms. The primary and secondary endpoints were dose-adjusted TAC trough level (L/D; ng/ml per mg/day) and TAC total daily dose (TDD; mg/day), respectively. Data were analyzed using generalized linear model analysis. CYP3A5 expressor status (yes/no), number of days post-Tx on the day of the TAC trough level, and/or diltiazem use (yes/no) were included as covariates in adjusted analyses.
Results: The study included n=76 HTx recipients receiving TAC (79% men; 82% white; 21% CYP3A5 expressors; age=53 ± 15 years; time post-Tx on day of TAC level=3226 ± 2075 days; mean TAC L/D=3.2 ± 1.6 ng/ml per mg/day; mean TAC TDD=2.98 ± 3.0 mg/day). In unadjusted analysis, TAC L/D and TAC TDD did not differ significantly between POR*1/*1 (n=40) and POR*28 carriers (n=36), p=0.17 and p=0.20, respectively. However, in adjusted analyses, TAC L/D was 20% higher in POR*28 carriers than in POR*1 homozygotes (p=0.06). TAC TDD was 24% lower in POR*28 carriers than in POR*1 homozygotes (p=0.047). POR*28 carrier status accounted for 4.9% and 5.4% of the variability in TAC L/D and TAC TDD, respectively.
Conclusion: POR*28 carrier status accounted for some of the variability in TAC disposition in HTx recipients who were greater than 1-year post-Tx. Additional studies are needed to evaluate the combined impact of CYP3A4, CYP3A5, and POR polymorphisms on TAC dose predictions and outcomes following HTx, particularly during the early post-Tx period. This work was funded, in part, by a grant from the American Heart Association (12GRNT12040211).
To cite this abstract in AMA style:
Alford T, Page R, Lindenfeld J, Aquilante C. Influence of POR*28 Genotype on Tacrolimus Disposition in Heart Transplant Recipients [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/influence-of-por28-genotype-on-tacrolimus-disposition-in-heart-transplant-recipients/. Accessed May 12, 2025.« Back to 2015 American Transplant Congress