ArticleTransplantation2011
Novel polymorphisms associated with tacrolimus trough concentrations: results from a multicenter kidney transplant consortium.
Article in Transplantation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers, 1 of them a synthesis that pooled it.
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Who cites it
77 citing papers in PubMed, 1 synthesis or guideline pooled it, 167 citations in OpenAlex.
- Racial and ethnic disparities in outcomes after heart transplantation: A systematic review of contributing factors and future directions to close the outcomes gap.The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation · 2016Pooled it
- Influence of TLR4 rs1927907 locus polymorphisms on tacrolimus pharmacokinetics in the early stage after liver transplantation.European journal of clinical pharmacology · 2014Trial
- Multidrug resistance-associated protein 2 (MRP2/ABCC2) haplotypes significantly affect the pharmacokinetics of tacrolimus in kidney transplant recipients.Clinical pharmacokinetics · 2013Trial
- Conversion from twice-daily tacrolimus capsules to once-daily extended-release tacrolimus (LCPT): a phase 2 trial of stable renal transplant recipients.Transplantation · 2013Trial
- Steroid-tacrolimus drug-drug interaction and the effect of CYP3A genotypes.British journal of clinical pharmacology · 2024Article
- The Impact ofJournal of personalized medicine · 2024Article
- Tacrolimus Dose Requirement inTransplant international : official journal of the European Society for Organ Transplantation · 2024Article
- Pharmacogenomic Analysis of CYP3A5*3 and Tacrolimus Trough Concentrations in Vietnamese Renal Transplant Outcomes.Pharmacogenomics and personalized medicine · 2024Article
- Towards Allograft Longevity: Leveraging Omics Technologies to Improve Heart Transplant Outcomes.Current heart failure reports · 2023Review
- The effects of the CYP3A5*3 variant on tacrolimus pharmacokinetics and outcomes in Tunisian kidney transplant recipients.La Tunisie medicale · 2023Article
- The impact of CYP3A4 and CYP3A5 genetic variations on tacrolimus treatment of living-donor Egyptian kidney transplanted patients.Journal of clinical laboratory analysis · 2023Article
- Comparison of Tacrolimus Intra-Patient Variability during 6-12 Months after Kidney Transplantation between CYP3A5 Expressers and Nonexpressers.Journal of clinical medicine · 2022Article
- Insights into the Pharmacogenetics of Tacrolimus Pharmacokinetics and Pharmacodynamics.Pharmaceutics · 2022Review
- Use of Pharmacogenetics to Optimize Immunosuppressant Therapy in Kidney-Transplanted Patients.Biomedicines · 2022Review
- Tacrolimus CYP3A Single-Nucleotide Polymorphisms and Preformed T- and B-Cell Alloimmune Memory Improve Current Pretransplant Rejection-Risk Stratification in Kidney Transplantation.Frontiers in immunology · 2022Article
- Precision Dosing for Tacrolimus Using Genotypes and Clinical Factors in Kidney Transplant Recipients of European Ancestry.Journal of clinical pharmacology · 2021Observational
- Cost-effectiveness of once-daily vs twice-daily tacrolimus among Hispanic and Black kidney transplant recipients.Journal of managed care & specialty pharmacy · 2021Article
- Chronic Inflammatory Status Observed in Patients with Type 2 Diabetes Induces Modulation of Cytochrome P450 Expression and Activity.International journal of molecular sciences · 2021Review
- Precision Medicine in Kidney Transplantation: Just Hype or a Realistic Hope?Transplantation direct · 2021Article
- Pharmacogenomics in kidney transplant recipients and potential for integration into practice.Journal of clinical pharmacy and therapeutics · 2020Observational
17 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundThe CYP4503A5*1 genotype is associated with lower tacrolimus concentrations. Although its effect is important, it incompletely explains the variability in tacrolimus concentrations and has a relatively low minor allele frequency in whites relative to African Americans (AA).
methodsWe studied clinical and recipient genetic correlates of dose-normalized tacrolimus troughs (n=12,277) in the first 6 months posttransplant using a customized single-nucleotide polymorphism chip with 2722 variants in a large, ethnically diverse (144 AA and 551 non-AA) adult kidney transplant population through a seven-center consortium.
resultsDuring the 6-month study, AAs had consistently lower median (interquartile range) troughs than non-AAs, 6.2 (4.4-8.4) ng/mL vs. 8.3 (6.4-10.4) ng/mL (P<0.0001), despite 60% higher daily doses, 8 (5-10) mg vs. 5 (4-7) mg (P<0.0001). The median tacrolimus trough concentration in week 1 posttransplant was particularly low in AAs (2.1 [1.2-3.5] ng/mL) compared with non-AAs (5.0 [3.1-8.2] ng/mL) (P<0.0001), despite similar initial doses. In single-variant analysis, CYP3A5*3 (rs776746) was the top variant (P=2.4×10) associated with troughs. After adjustment for CYP3A5*3, clinical factors and race, 35 additional variants were identified (P<0.01, not significant at false discovery rate 20%). In the final multivariant, regression models beginning with these variants and clinical factors, seven variants were identified in the non-AA and seven variants in the AA group towards the first trough concentrations. Rs776746 (CYP3A5), rs2239393 (COMT) and diabetes were the only factors common in both populations.
conclusionWe identified variants beyond CYP3A5*3, which may further explain pharmacokinetic variability of tacrolimus and demonstrated that important variants differ by race.
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