scholarly journals Predictive Modeling of Tacrolimus Dose Requirement Based on High-Throughput Genetic Screening

2016 ◽  
Vol 17 (4) ◽  
pp. 1008-1019 ◽  
Author(s):  
C. Damon ◽  
M. Luck ◽  
L. Toullec ◽  
I. Etienne ◽  
M. Buchler ◽  
...  
Keyword(s):  
Predictive Modeling ◽  
High Throughput ◽  
Genetic Screening ◽  
Dose Requirement ◽  
Tacrolimus Dose

scholarly journals Genetic Screening for Mutants with Altered Seminal Root Numbers in Hexaploid Wheat Using a High-Throughput Root Phenotyping Platform

2019 ◽  
Vol 9 (9) ◽  
pp. 2799-2809 ◽  
Author(s):  
Oluwaseyi Shorinola ◽  
Ryan Kaye ◽  
Guy Golan ◽  
Zvi Peleg ◽  
Stefan Kepinski ◽  
...  
Keyword(s):  
High Throughput ◽  
Genetic Screening ◽  
Hexaploid Wheat ◽  
Seminal Root ◽  
Root Numbers ◽  
Root Phenotyping

Tacrolimus dose requirement in pediatric liver transplantation: influence of CYP3A5 gene polymorphism

2013 ◽  
Vol 14 (9) ◽  
pp. 1017-1025 ◽  
Author(s):  
Philippe Durand ◽  
Dominique Debray ◽  
Mikaela Kolaci ◽  
Jerome Bouligand ◽  
Valérie Furlan ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Gene Polymorphism ◽  
Pediatric Liver Transplantation ◽  
Dose Requirement ◽  
Pediatric Liver ◽  
Cyp3a5 Gene ◽  
Tacrolimus Dose

scholarly journals A Genome-Scale Vector Resource Enables High-Throughput Reverse Genetic Screening in a Malaria Parasite

2015 ◽  
Vol 17 (3) ◽  
pp. 404-413 ◽  
Author(s):  
Ana Rita Gomes ◽  
Ellen Bushell ◽  
Frank Schwach ◽  
Gareth Girling ◽  
Burcu Anar ◽  
...  
Keyword(s):  
High Throughput ◽  
Genetic Screening ◽  
Malaria Parasite ◽  
Reverse Genetic ◽  
A Genome ◽  
Genome Scale

MP25-09 HIGH THROUGHPUT GENETIC SCREENING WITH DROSOPHILA MELANOGASTER IDENTIFIES NOVEL GENES ASSOCIATED WITH STONE FORMATION

2014 ◽  
Vol 191 (4S) ◽  
Author(s):  
Thomas Chi ◽  
Man Su Kim ◽  
Sven Lang ◽  
Tiffany Zee ◽  
Gulinuer Muteliefu ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
High Throughput ◽  
Genetic Screening ◽  
Stone Formation ◽  
Novel Genes

scholarly journals Diagnostic effectiveness of transforming growth factor beta 1 (TGF-β1) at adjustment of tacrolimus individual dose in pediatric liver recipients

2019 ◽  
Vol 20 (4) ◽  
pp. 38-43
Author(s):  
R. M. Kurabekova ◽  
O. M. Tsiroulnikova ◽  
O. E. Gichkun ◽  
I. E. Pashkova ◽  
G. A. Olefirenko ◽  
...  
Keyword(s):  
Blood Level ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Cytokine Level ◽  
Dose Requirement ◽  
Diagnostic Efficacy ◽  
Growth Factor Beta ◽  
Tacrolimus Dose ◽  
Tacrolimus Blood Concentration ◽  
Tgf Β1

Blood level of transforming growth factor beta 1 (TGF-β1) is associated with liver function and immune homeostasis, which suggests it as a potential biomarker for immunosuppressant tacrolimus dose requirement at liver transplantation (LT).Aim.To evaluate diagnostic efficacy of TGF-β1 blood level at determination of individual tacrolimus dose requirement in children at LT.Materials and methods.89 children with end stage liver disease aged from 3 to 73 months were examined. Children underwent living related LT, then the recipients received 2–3 component immunosuppressive therapy, including tacrolimus. Blood concentration of tacrolimus and TGF-β1 was measured by ELISA.Results.TGF-β1 blood level in children before LT was significantly lower than in healthy children: 3.7 (1.3–8.4) and 19.3 (12.6–25.5) ng/ml, p = 0.001. A month after LT, its concentration increased to 8.1 (1.8–15.3) ng/ml (p = 0.02). A year after LT, the cytokine level remained higher than before transplantation: 6.6 (1.9–12.6) ng/ml, p = 0.01. TGF-β1 level did not correlate with tacrolimus blood concentration, determined 12 hours after the last administration of the drug, neither a month, nor a year after transplantation. At the same time, the cytokine level one month after LT was associated with a tacrolimus daily dose one year after the operation (r = –0.23, p = 0.04). In the recipients, who received smaller daily doses (0.4–2.5 mg) of tacrolimus, TGF-β1 level was higher than in those receiving large doses (3.0–6.0 mg) of the drug: 9.1 (2.6–16.2) ng/ml vs. 4.2 (1.3–9.2) ng/ ml, p = 0.04. Evaluation of diagnostic efficacy of the TGF-β1 level as a test for the detection of tacrolimus dose requirement showed that the area under the ROC curve (AUC) was 0.66 ± 0.07; 95% CI [0.53–0.79], the sensitivity and specificity of the test were 60 and 74% at threshold value 6.7 ng/ml. Relative risk of higher tacrolimus dose requirement was 3.14 ± 0.48; 95% CI [1.24–7.96].Conclusion.TGF-β1 blood level in one month after LT less than 6.7 ng/ml is 3 times higher risk factor of tacrolimus dose requirement more than 3.0 mg per day. The likehood of the test is 66%, the sensitivity and specificity – 60 and 74%.

scholarly journals CYP3A-status is associated with blood concentration and dose-requirement of tacrolimus in heart transplant recipients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Máté Déri ◽  
Zsófia Szakál-Tóth ◽  
Ferenc Fekete ◽  
Katalin Mangó ◽  
Evelyn Incze ◽  
...  
Keyword(s):  
Heart Transplant ◽  
Blood Concentration ◽  
High Dose ◽  
Transplant Recipients ◽  
Dose Requirement ◽  
Post Operative Period ◽  
Heart Transplant Recipients ◽  
Tacrolimus Dose ◽  
Tacrolimus Blood Concentration ◽  
Cyp3a4 Expression

AbstractHigh inter-individual variability in tacrolimus clearance is attributed to genetic polymorphisms of CYP3A enzymes. However, due to CYP3A phenoconversion induced by non-genetic factors, continuous changes in tacrolimus-metabolizing capacity entail frequent dose-refinement for optimal immunosuppression. In heart transplant recipients, the contribution of patients’ CYP3A-status (CYP3A5 genotype and CYP3A4 expression) to tacrolimus blood concentration and dose-requirement was evaluated in the early and late post-operative period. In low CYP3A4 expressers carrying CYP3A5*3/*3, the dose-corrected tacrolimus level was significantly higher than in normal CYP3A4 expressers or in those with CYP3A5*1. Modification of the initial tacrolimus dose was required for all patients: dose reduction by 20% for low CYP3A4 expressers, a 40% increase for normal expressers and a 2.4-fold increase for CYP3A5*1 carriers. The perioperative high-dose corticosteroid therapy was assumed to ameliorate the low initial tacrolimus-metabolizing capacity during the first month. The fluctuation of CYP3A4 expression and tacrolimus blood concentration (C0/D) was found to be associated with tapering and cessation of corticosteroid in CYP3A5 non-expressers, but not in those carrying CYP3A5*1. Although monitoring of tacrolimus blood concentration cannot be omitted, assaying recipients’ CYP3A-status can guide optimization of the initial tacrolimus dose, and can facilitate personalized tacrolimus therapy during steroid withdrawal in the late post-operative period.

scholarly journals Tacrolimus dose requirement based on the CYP3A5 genotype in renal transplant patients

Oncotarget ◽  
2017 ◽  
Vol 8 (46) ◽  
pp. 81285-81294 ◽  
Author(s):  
Lihui Qu ◽  
Yingying Lu ◽  
Meike Ying ◽  
Bingjue Li ◽  
Chunhua Weng ◽  
...  
Keyword(s):  
Renal Transplant ◽  
Dose Requirement ◽  
Transplant Patients ◽  
Cyp3a5 Genotype ◽  
Renal Transplant Patients ◽  
Tacrolimus Dose
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