ArticlePharmacogenetics and genomics2008
Role of cytochrome P450 2C8 and 2J2 genotypes in calcineurin inhibitor-induced chronic kidney disease.
Article in Pharmacogenetics and genomics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
33 citing papers in PubMed, 63 citations in OpenAlex.
- Exploring genetic and non-genetic risk factors for delayed graft function, acute and subclinical rejection in renal transplant recipients.British journal of clinical pharmacology · 2016Trial
- Genetic markers in the EET metabolic pathway are associated with outcomes in patients with aneurysmal subarachnoid hemorrhage.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2015Trial
- Drug-Drug Interactions Between Oral Anticoagulants and Calcineurin Inhibitors in Nephrotic Syndrome for Management of Thromboembolism.Biomedicines · 2026Review
- Association of CYP3A5, ABCB1, and CYP2C8 Polymorphisms with Renal Function in Kidney Transplant Recipients Receiving Tacrolimus.European journal of drug metabolism and pharmacokinetics · 2025Article
- Role of Arachidonic Acid and Its Metabolites in the Biological and Clinical Manifestations of Idiopathic Nephrotic Syndrome.International journal of molecular sciences · 2021Review
- Association Between Variants in Calcineurin Inhibitor Pharmacokinetic and Pharmacodynamic Genes and Renal Dysfunction in Adult Heart Transplant Recipients.Frontiers in genetics · 2021Article
- Identification of genetic variants associated with tacrolimus metabolism in kidney transplant recipients by extreme phenotype sampling and next generation sequencing.The pharmacogenomics journal · 2019Observational
- Polymorphisms in vasoactive eicosanoid genes of kidney donors affect biopsy scores and clinical outcomes in renal transplantation.PloS one · 2019Article
- Oxylipin profiling of human plasma reflects the renal dysfunction in uremic patients.Metabolomics : Official journal of the Metabolomic Society · 2018Article
- Tacrolimus Elimination in Four Patients With a CYP3A5*3/*3 CYP3A4*22/*22 Genotype Combination.Pharmacotherapy · 2018Article
- Formation of Both Heme and Apoprotein Adducts Contributes to the Mechanism-Based Inactivation of Human CYP2J2 by 17Drug metabolism and disposition: the biological fate of chemicals · 2018Article
- Prediction of olanzapine exposure in individual patients using physiologically based pharmacokinetic modelling and simulation.British journal of clinical pharmacology · 2018Article
- Translational medical research and liver transplantation: systematic review.Translational gastroenterology and hepatology · 2018Review
- Pharmacokinetics, Pharmacodynamics and Pharmacogenetics of Tacrolimus in Kidney Transplantation.Current drug metabolism · 2018Review
- Effect of Cytochrome P450 Metabolites of Arachidonic Acid in Nephrology.Journal of the American Society of Nephrology : JASN · 2017Review
- Heme Modification Contributes to the Mechanism-Based Inactivation of Human Cytochrome P450 2J2 by Two Terminal Acetylenic Compounds.Drug metabolism and disposition: the biological fate of chemicals · 2017Article
- The 6R's of drug induced nephrotoxicity.BMC nephrology · 2017Review
- Metabolism of Anandamide by Human Cytochrome P450 2J2 in the Reconstituted System and Human Intestinal Microsomes.The Journal of pharmacology and experimental therapeutics · 2016Article
- The role of pharmacogenetics in the disposition of and response to tacrolimus in solid organ transplantation.Clinical pharmacokinetics · 2014Review
- Pharmacogenetic considerations for optimizing tacrolimus dosing in liver and kidney transplant patients.World journal of gastroenterology · 2013Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 4 countries.
Funding
Abstract
objectivesThe calcineurin inhibitors (CNIs) cyclosporine A (CsA) and tacrolimus (Tac) help prevent allograft rejection but are associated with nephrotoxicity. Cytochrome P450 2C8 (CYP2C8) and CYP2J2 are polymorphic enzymes expressed in the kidney that metabolize arachidonic acid (AA) to epoxyeicosatrienoic acids, promoting kidney homeostasis. This study examined the association between CNI-induced nephrotoxicity in liver transplant patients and CYP2C8 and CYP2J2 polymorphisms.
methodsLiver transplantation patients receiving CNIs for at least 3 years were genotyped for CYP2C8*3, CYP2C8*4, CYP2C8 Haplotypes B and C, and CYP2J2*7 and evaluated for nephrotoxicity (serum creatinine > or = 1.6 mg/dl) 3-year post-transplantation. CYP2C8 proteins were also engineered in E. coli and their activity towards AA and inhibition by CNIs was investigated in vitro.
resultsThe risk of kidney disease post-transplantation was positively associated with CYP2C8*3 genotype. Odds ratios for all participants carrying at least one CYP2C8*3 allele were significant [odds ratio=2.38 (1.19-4.78)]. Stratification by CNI indicated a significant association between CYP2C8*3 and nephrotoxicity among patients receiving Tac but not CsA. The risk of renal dysfunction was not significantly influenced by CYP2C8*4, CYP2J2*7, or CYP2C8 haplotype B genotypes although inheritance of haplotype C seems to be protective. In vitro, the gene products of CYP2C8*3 and CYP2C8*4 were deficient in AA epoxidation, retaining 26 and 18% of wild-type activity, respectively. Circulating plasma concentrations of CsA and Tac inhibited CYP2C8 wild-type in vitro epoxidation of AA by 17 and 35%, respectively.
conclusionInheritance of CYP2C8*3 is associated with a higher risk of developing renal toxicity in patients treated chronically with CNIs, and especially Tac, possibly by reducing formation of kidney protecting vasodilatory epoxyeicosatrienoic acids.
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