ArticleActa pharmacologica Sinica2017
IL-3 and CTLA4 gene polymorphisms may influence the tacrolimus dose requirement in Chinese kidney transplant recipients.
Article in Acta pharmacologica Sinica, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 29 citations in OpenAlex.
- Effects of CYP3A4, CYP3A5, and ABCB1 genetic variants on tacrolimus metabolism during the early period after kidney transplantation.The pharmacogenomics journal · 2026Article
- Trends in Precision Medicine and Pharmacogenetics as an Adjuvant in Establishing a Correct Immunosuppressive Therapy for Kidney Transplant: An Up-to-Date Historical Overview.International journal of molecular sciences · 2025Review
- Pharmacogenomics of Old and New Immunosuppressive Drugs for Precision Medicine in Kidney Transplantation.Journal of clinical medicine · 2023Review
- Tacrolimus pharmacokinetics in pediatric nephrotic syndrome: A combination of population pharmacokinetic modelling and machine learning approaches to improve individual prediction.Frontiers in pharmacology · 2022Article
- Prediction of Tacrolimus Dose/Weight-Adjusted Trough Concentration in Pediatric Refractory Nephrotic Syndrome: A Machine Learning Approach.Pharmacogenomics and personalized medicine · 2022Article
- Population Pharmacokinetic Modelling for Nifedipine to Evaluate the Effect of Parathyroid Hormone on CYP3A in Patients with Chronic Kidney Disease.Drug design, development and therapy · 2022Article
- The impact of IL-10 and CYP3A5 gene polymorphisms on dose-adjusted trough blood tacrolimus concentrations in early post-renal transplant recipients.Pharmacological reports : PR · 2021Article
- Characterization of CYP3A pharmacogenetic variation in American Indian and Alaska Native communities, targeting CYP3A4*1G allele function.Clinical and translational science · 2021Observational
- Functional CYP3A variants affecting tacrolimus trough blood concentrations in Chinese renal transplant recipients.The pharmacogenomics journal · 2021Article
- Effect of the Most Relevant CYP3A4 and CYP3A5 Polymorphisms on the Pharmacokinetic Parameters of 10 CYP3A Substrates.Biomedicines · 2020Article
- Impact of single nucleotide polymorphisms on P450 oxidoreductase and peroxisome proliferator-activated receptor alpha on tacrolimus pharmacokinetics in renal transplant recipients.The pharmacogenomics journal · 2019Article
- Article
- Whole exome sequencing for the identification of CYP3A7 variants associated with tacrolimus concentrations in kidney transplant patients.Scientific reports · 2018Article
- Attempted validation of 44 reported SNPs associated with tacrolimus troughs in a cohort of kidney allograft recipients.Pharmacogenomics · 2018Article
- Pharmacokinetics, Pharmacodynamics and Pharmacogenetics of Tacrolimus in Kidney Transplantation.Current drug metabolism · 2018Review
- Pharmacogenetics to optimize immunosuppressant therapy in systemic lupus erythematosus: a scoping review.PharmacogenomicsArticle
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Authors and funding
14 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The highly variable pharmacokinetics and narrow therapeutic window of tacrolimus (TAC) has hampered its clinical use. Genetic polymorphisms may contribute to the variable response, but the evidence is not compelling, and the explanation is unclear. In this study we attempted to find previously unknown genetic factors that may influence the TAC dose requirements. The association of 105 pathway-related single nucleotide polymorphisms (SNPs) with TAC dose-adjusted concentrations (C0/D) was examined at 7, 30 and 90 d post-operation in 382 Chinese kidney transplant recipients. In CYP3A5 non-expressers, the patients carrying the IL-3 rs181781 AA genotype showed a significantly higher TAC logC0/D than those with the AG genotype at 30 and 90 d post-operation (AA vs AG, 2.21±0.06 vs 2.01±0.03, P=0.004; and 2.17±0.06 vs 2.03±0.03, P=0.033, respectively), and than those with the GG genotype at 30 d (AA vs GG, 2.21±0.06 vs 2.04±0.03, P =0.011). At 30 d, the TAC logC0/D in the grouped AG+GG genotypes of CTLA4 rs4553808 was significantly lower than that in the AA genotype (P =0.041) in CYP3A5 expressers, but it was higher (P=0.008) in the non-expressers. We further validated the influence of CYP3A5 rs776746, CYP3A4 rs2242480 and rs4646437 on the TAC C0/D; other candidate SNPs were not associated with the differences in TAC C0/D. In conclusion, genetic polymorphisms in the immune genes IL-3 rs181781 and CTLA4 rs4553808 may influence the TAC C0/D. They may, together with CYP3A5 rs776746, CYP3A4 rs2242480 and rs4646437, contribute to the variation in TAC dose requirements. When conducting individualized therapy with tacrolimus, these genetic factors should be taken into account.
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