Whole Exome Sequencing for the Identification of CYP3A7 Variants Associated with Tacrolimus Concentrations in Kidney Transplant Patients

Overview

Journal Sci Rep

Specialty Science

Date 2018 Dec 26

PMID 30584253

Citations 10

Authors

Minji Sohn

Myeong Gyu Kim

Nayoung Han

In-Wha Kim

Jungsoo Gim

Sang-Il Min

Eun Young Song

Yon Su Kim

Hun Soon Jung

Young Kee Shin

Jongwon Ha

Jung Mi Oh

Affiliations

Soon will be listed here.

Abstract

The purpose of this study was to identify genotypes associated with dose-adjusted tacrolimus trough concentrations (C/D) in kidney transplant recipients using whole-exome sequencing (WES). This study included 147 patients administered tacrolimus, including seventy-five patients in the discovery set and seventy-two patients in the replication set. The patient genomes in the discovery set were sequenced using WES. Also, known tacrolimus pharmacokinetics-related intron variants were genotyped. Tacrolimus C/D was log-transformed. Sixteen variants were identified including novel CYP3A7 rs12360 and rs10211 by ANOVA. CYP3A7 rs2257401 was found to be the most significant variant among the periods by ANOVA. Seven variants including CYP3A7 rs2257401, rs12360, and rs10211 were analyzed by SNaPshot in the replication set and the effects on tacrolimus C/D were verified. A linear mixed model (LMM) was further performed to account for the effects of the variants and clinical factors. The combined set LMM showed that only CYP3A7 rs2257401 was associated with tacrolimus C/D after adjusting for patient age, albumin, and creatinine. The CYP3A7 rs2257401 genotype variant showed a significant difference on the tacrolimus C/D in those expressing CYP3A5, showing its own effect. The results suggest that CYP3A7 rs2257401 may serve as a significant genetic marker for tacrolimus pharmacokinetics in kidney transplantation.

Citing Articles

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