Multigene Predictors of Tacrolimus Exposure in Kidney Transplant Recipients

Overview

Journal Pharmacogenomics

Specialties Genetics
Pharmacology

Date 2015 Jun 13

PMID 26067485

Citations 17

Authors

Rebecca A Pulk

David S Schladt

William S Oetting

Weihua Guan

Ajay K Israni

Arthur J Matas

Rory P Remmel

Pamala A Jacobson

Affiliations

Soon will be listed here.

Abstract

Aim: Determine the effect of the genetic variants beyond CYP3A5*3 on tacrolimus disposition.

Patients & Methods: We studied genetic correlates of tacrolimus trough concentrations with POR*28, CYP3A4*22 and ABCC2 haplotypes in a large, ethnically diverse kidney transplant cohort (n = 2008).

Results: Subjects carrying one or more CYP3A5*1 alleles had lower tacrolimus trough concentrations (p = 9.2 × 10(-75)). The presence of one or two POR*28 alleles was associated with a 4.63% reduction in tacrolimus trough concentrations after adjusting for CYP3A5*1 and clinical factors (p = 0.037). In subset analyses, POR*28 was significant only in CYP3A5*3/*3 carriers (p = 0.03). The CYP3A4*22 variant and the ABBC2 haplotypes were not associated.

Conclusion: This study confirmed that CYP3A5*1 was associated with lower tacrolimus trough concentrations. POR*28 was associated with decreased tacrolimus trough concentrations although the effect was small possibly through enhanced CYP3A4 enzyme activity. CYP3A4*22 and ABCC2 haplotypes did not influence tacrolimus trough concentrations. Original submitted 19 December 2014; Revision submitted 2 April 2015.

Citing Articles

Interaction between tacrolimus and calcium channel blockers based on CYP3A5 genotype in Chinese renal transplant recipients.

Zong H, Zhang Y, Liu F, Zhang X, Yang Y, Cao X Front Pharmacol. 2024; 15:1458838.

PMID: 39268459 PMC: 11390670. DOI: 10.3389/fphar.2024.1458838.

The impact of CYP3A4 and CYP3A5 genetic variations on tacrolimus treatment of living-donor Egyptian kidney transplanted patients.

Wanas H, Kamel M, William E, Fayad T, Abdelfattah M, Elbadawy H J Clin Lab Anal. 2023; 37(19-20):e24969.

PMID: 37789683 PMC: 10681408. DOI: 10.1002/jcla.24969.

Genetic Polymorphisms Affecting Tacrolimus Metabolism and the Relationship to Post-Transplant Outcomes in Kidney Transplant Recipients.

Cheng F, Li Q, Wang J, Hu M, Zeng F, Wang Z Pharmgenomics Pers Med. 2021; 14:1463-1474.

PMID: 34824543 PMC: 8610755. DOI: 10.2147/PGPM.S337947.

Genotyping in Clinical Practice: Ready for Implementation?.

Mulder T, van Eerden R, de With M, Elens L, Hesselink D, Matic M Front Genet. 2021; 12:711943.

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A review of clinical pharmacogenetics Studies in African populations.

Radouani F, Zass L, Hamdi Y, da Rocha J, Sallam R, Abdelhak S Per Med. 2020; 17(2):155-170.

PMID: 32125935 PMC: 8093600. DOI: 10.2217/pme-2019-0110.

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