Whole exome sequencing for the identification of CYP3A7 variants associated with tacrolimus concentrations in kidney transplant patients
Abstract The purpose of this study was to identify genotypes associated with dose-adjusted tacrolimus trough concentrations (C0/D) in kidney transplant recipients using whole-exome sequencing (WES). This study included 147 patients administered tacrolimus, including seventy-five patients in the disc...
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Nature Portfolio
2018
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oai:doaj.org-article:8957da4f57f14db5b4a9a5980b9a67542021-12-02T15:09:12ZWhole exome sequencing for the identification of CYP3A7 variants associated with tacrolimus concentrations in kidney transplant patients10.1038/s41598-018-36085-w2045-2322https://doaj.org/article/8957da4f57f14db5b4a9a5980b9a67542018-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-36085-whttps://doaj.org/toc/2045-2322Abstract The purpose of this study was to identify genotypes associated with dose-adjusted tacrolimus trough concentrations (C0/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 C0/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 C0/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 C0/D after adjusting for patient age, albumin, and creatinine. The CYP3A7 rs2257401 genotype variant showed a significant difference on the tacrolimus C0/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.Minji SohnMyeong Gyu KimNayoung HanIn-Wha KimJungsoo GimSang-Il MinEun Young SongYon Su KimHun Soon JungYoung Kee ShinJongwon HaJung Mi OhNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-10 (2018) |
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Medicine R Science Q 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 Whole exome sequencing for the identification of CYP3A7 variants associated with tacrolimus concentrations in kidney transplant patients |
| description |
Abstract The purpose of this study was to identify genotypes associated with dose-adjusted tacrolimus trough concentrations (C0/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 C0/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 C0/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 C0/D after adjusting for patient age, albumin, and creatinine. The CYP3A7 rs2257401 genotype variant showed a significant difference on the tacrolimus C0/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 |
article |
| author |
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 |
| author_facet |
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 |
| author_sort |
Minji Sohn |
| title |
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_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_sort |
whole exome sequencing for the identification of cyp3a7 variants associated with tacrolimus concentrations in kidney transplant patients |
| publisher |
Nature Portfolio |
| publishDate |
2018 |
| url |
https://doaj.org/article/8957da4f57f14db5b4a9a5980b9a6754 |
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