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Whole exome sequencing for the identification of CYP3A7 variants associated with tacrolimus concentrations in kidney transplant patients
The purpose of this study was to identify genotypes associated with dose-adjusted tacrolimus trough concentrations (C(0)/D) in kidney transplant recipients using whole-exome sequencing (WES). This study included 147 patients administered tacrolimus, including seventy-five patients in the discovery s...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6305386/ https://www.ncbi.nlm.nih.gov/pubmed/30584253 http://dx.doi.org/10.1038/s41598-018-36085-w |
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author | Sohn, Minji Kim, Myeong Gyu Han, Nayoung Kim, In-Wha Gim, Jungsoo Min, Sang-Il Song, Eun Young Kim, Yon Su Jung, Hun Soon Shin, Young Kee Ha, Jongwon Oh, Jung Mi |
author_facet | Sohn, Minji Kim, Myeong Gyu Han, Nayoung Kim, In-Wha Gim, Jungsoo Min, Sang-Il Song, Eun Young Kim, Yon Su Jung, Hun Soon Shin, Young Kee Ha, Jongwon Oh, Jung Mi |
author_sort | Sohn, Minji |
collection | PubMed |
description | The purpose of this study was to identify genotypes associated with dose-adjusted tacrolimus trough concentrations (C(0)/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(0)/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(0)/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(0)/D after adjusting for patient age, albumin, and creatinine. The CYP3A7 rs2257401 genotype variant showed a significant difference on the tacrolimus C(0)/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. |
format | Online Article Text |
id | pubmed-6305386 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-63053862018-12-31 Whole exome sequencing for the identification of CYP3A7 variants associated with tacrolimus concentrations in kidney transplant patients Sohn, Minji Kim, Myeong Gyu Han, Nayoung Kim, In-Wha Gim, Jungsoo Min, Sang-Il Song, Eun Young Kim, Yon Su Jung, Hun Soon Shin, Young Kee Ha, Jongwon Oh, Jung Mi Sci Rep Article The purpose of this study was to identify genotypes associated with dose-adjusted tacrolimus trough concentrations (C(0)/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(0)/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(0)/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(0)/D after adjusting for patient age, albumin, and creatinine. The CYP3A7 rs2257401 genotype variant showed a significant difference on the tacrolimus C(0)/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. Nature Publishing Group UK 2018-12-24 /pmc/articles/PMC6305386/ /pubmed/30584253 http://dx.doi.org/10.1038/s41598-018-36085-w Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Sohn, Minji Kim, Myeong Gyu Han, Nayoung Kim, In-Wha Gim, Jungsoo Min, Sang-Il Song, Eun Young Kim, Yon Su Jung, Hun Soon Shin, Young Kee Ha, Jongwon Oh, Jung Mi Whole exome sequencing for the identification of CYP3A7 variants associated with tacrolimus concentrations in kidney transplant patients |
title | Whole exome sequencing for the identification of CYP3A7 variants associated with tacrolimus concentrations in kidney transplant patients |
title_full | Whole exome sequencing for the identification of CYP3A7 variants associated with tacrolimus concentrations in kidney transplant patients |
title_fullStr | Whole exome sequencing for the identification of CYP3A7 variants associated with tacrolimus concentrations in kidney transplant patients |
title_full_unstemmed | Whole exome sequencing for the identification of CYP3A7 variants associated with tacrolimus concentrations in kidney transplant patients |
title_short | Whole exome sequencing for the identification of CYP3A7 variants associated with tacrolimus concentrations in kidney transplant patients |
title_sort | whole exome sequencing for the identification of cyp3a7 variants associated with tacrolimus concentrations in kidney transplant patients |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6305386/ https://www.ncbi.nlm.nih.gov/pubmed/30584253 http://dx.doi.org/10.1038/s41598-018-36085-w |
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