| Clinical significance and gene prediction of a novel classification system based on tacrolimus concentration-to-dose ratio in the early post-liver transplant period |
| 论文作者 |
Fan, JW; Wen, PH; Yuan, LY; Xia, Y; Hu, SJ; Zhang, XQ; Peng, ZH |
| 期刊/会议名称 |
FRONTIERS IN PHARMACOLOGY |
| 论文年度 |
2025 |
| 论文类别 |
|
| 摘要 |
Background and Aims Classification system of tacrolimus elimination and its clinical significance has not been well described in liver transplantation. This study aimed to present a novel tacrolimus clearance clinical-FIS (Fast-Intermediate-Slow) classification and its gene prediction system.Methods Patients from 3 transplant centers were enrolled in this study. All recipients and their corresponding donor livers from center 1 were genotyped using an Affymetrix DMET Plus microarray, and association analysis was performed using trough blood concentration/weight-adjusted-dose ratios (CDR, (ng/mL)/(mg/kg)). The candidate-associated loci were then sequenced in center 2 and center 3 patients for verification.Results A clinical classification based on tacrolimus CDR can effectively divide liver transplantation patients into fast elimination (FE), intermediate elimination (IE), and slow elimination (SE) groups, which we called the clinical-FIS classification. Trough blood concentrations in the clinical-SE group during the early postoperative period were higher than those in the clinical-FE and clinical-IE groups, which could lead to delayed recovery of liver (P = 0.0373) and kidney function (P = 0.0135) and a higher infection rate (P = 0.0086). The prediction accuracy of the current CPIC (Clinical Pharmacogenetics Implementation Consortium)-EIP metabolizer classification based on recipient CYP3A5 rs776746 genotype for clinical-FIS classification was only 35.56%. A newly established genetic-EIP classification including major effect genetic factors (donor and recipient CYP3A5 rs776746) and minor effect genetic factors (recipient SULT1E1 rs3775770 and donor SLC7A8 rs7141505) showed 73.2% overall consistency with the former clinical FIS classification.Conclusion Our study presented a novel tacrolimus clearance classification, clinical-FIS, and then proposed a novel prospective genetic-EIP classification as a genotyping basis for precisely predicting the clinical-FIS. |
| 卷 |
16 |
| 影响因子 |
4.8 |
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