CYP3A7, CYP3A4, and CYP3A5 genetic polymorphisms in recipients rather than donors influence tacrolimus concentrations in the early stages after liver transplantation

Dong, Yue; Xu, Qinxia; Li, Ruidong; Tao, Yue; Zhang, Quanbao; Li, Jianhua; Ma, Zhenyu; Chen, Shen; Zhong, Ming; Wang, Zhengxin; Qiu, Xiaoyan

doi:10.1016/j.gene.2021.146007

Cited by 16 publications

(7 citation statements)

References 39 publications

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“…Candidate single nucleotide polymorphisms (SNPs) were mainly selected from previously reported literature, which may potentially affect tacrolimus pharmacokinetics in solid‐organ transplantation. All SNPs and their respective genes analyzed in this study are listed in Table S1 5,8,16–30 . For genotyping, briefly, a 0.5‐mL blood sample was collected and genomic DNA was extracted from ethylenediaminetetraacetic acid‐anticoagulated peripheral blood samples using a commercially available DNA purification kit (EasyPure Blood Genomic DNA Kit, Transgene Biotech).…”

Section: Methodsmentioning

confidence: 99%

“…All SNPs and their respective genes analyzed in this study are listed in Table S1. 5,8,[16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] For genotyping, briefly, a 0.5-mL blood sample was collected and genomic DNA was extracted from ethylenediaminetetraacetic acid-anticoagulated peripheral blood samples using a commercially available DNA purification kit (EasyPure Blood Genomic DNA Kit, Transgene Biotech). All samples with a call rate greater than 95% were genotyped using an Infinium Asian Screening Array-China Health Industry Alliance Bead chip (Illumina, Inc.) according to the Illumina Infinium HTS chip standard operating procedures.…”

Section: Genotypingmentioning

confidence: 99%

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Genotype‐Guided Model for Prediction of Tacrolimus Initial Dosing After Lung Transplantation

Du,

Wang,

Zhang

et al. 2024

The Journal of Clinical Pharma

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The determination of the appropriate initial dose for tacrolimus is crucial in achieving the target concentration promptly and avoiding adverse effects and poor prognosis. However, the trial‐and‐error approach is still common practice. This study aimed to establish a prediction model for an initial dosing algorithm of tacrolimus in patients receiving a lung transplant. A total of 210 lung transplant recipients were enrolled, and 26 single nucleotide polymorphisms (SNP) from 18 genes that could potentially affect tacrolimus pharmacokinetics were genotyped. Associations between SNPs and tacrolimus concentration/dose ratio were analyzed. SNPs that remained significant in pharmacogenomic analysis were further combined with clinical factors to construct a prediction model for tacrolimus initial dose. The dose needed to reach steady state tacrolimus concentrations and achieve the target range was used to validate model prediction efficiency. Our final model consisted of 7 predictors—CYP3A5 rs776746, SLCO1B3 rs4149117, SLC2A2 rs1499821, NFATc4 rs1955915, alanine aminotransferase, direct bilirubin, and hematocrit—and explained 41.4% variance in the tacrolimus concentration/dose ratio. It achieved an area under the receiver operating characteristic curve of 0.804 (95% confidence interval, 0.746‐0.861). The Hosmer‐Lemeshow test yielded a nonsignificant P value of .790, suggesting good fit of the model. The predicted dose exhibited good correlation with the observed dose in the early postoperative period (r = 0.748, P less than .001). Our study provided a genotype‐guided prediction model for tacrolimus initial dose, which may help to guide individualized dosing of tacrolimus in the lung transplant population in clinical practice.

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Section: Methodsmentioning

confidence: 99%

Section: Genotypingmentioning

confidence: 99%

Genotype‐Guided Model for Prediction of Tacrolimus Initial Dosing After Lung Transplantation

Du,

Wang,

Zhang

et al. 2024

The Journal of Clinical Pharma

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“…For instance, SNPs in the CYP3A4 and CYP3A5 genes, which encode the main tacrolimus-metabolizing enzymes, have been strongly linked to varying levels of drug metabolization, which helps determine the interindividual differences in tacrolimus pharmacokinetics after transplantation, so that dosing can be adjusted accordingly. 46 …”

Section: Genome-wide Association Studies In Solid Organ Transplantationmentioning

confidence: 99%

The Impact of Donor and Recipient Genetic Variation on Outcomes After Solid Organ Transplantation: A Scoping Review and Future Perspectives

Nieuwenhuis

Keating

et al. 2021

Transplantation

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“…In addition, there is influence of other enzymes in the CYP3A family, including CYP3A4 and CYP3A7. In a recent study of LT recipients, CYP3A7, CYP3A4, and CYP3A5*3 polymorphisms in the recipients and not the donors were associated with tacrolimus C0/D in the early post-transplant period [4].…”

mentioning

confidence: 91%

Role of pharmacogenetics and tacrolimus dosing in liver transplantation

Fung

2022

Hepatol Int

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CYP3A7, CYP3A4, and CYP3A5 genetic polymorphisms in recipients rather than donors influence tacrolimus concentrations in the early stages after liver transplantation

Cited by 16 publications

References 39 publications

Genotype‐Guided Model for Prediction of Tacrolimus Initial Dosing After Lung Transplantation

Genotype‐Guided Model for Prediction of Tacrolimus Initial Dosing After Lung Transplantation

The Impact of Donor and Recipient Genetic Variation on Outcomes After Solid Organ Transplantation: A Scoping Review and Future Perspectives

Role of pharmacogenetics and tacrolimus dosing in liver transplantation

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