Trial reportEuropean journal of clinical pharmacology2015
Association between interleukin-18 promoter variants and tacrolimus pharmacokinetics in Chinese renal transplant patients.
Trial report in European journal of clinical pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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The trial behind it
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Who cites it
7 citing papers in PubMed, 9 citations in OpenAlex.
- A Novel Laboratory-Developed Test Using Multiplex qPCR to Further Personalize Tacrolimus Dosing.International journal of molecular sciences · 2026Article
- A systematic review and meta-analysis recite the efficacy of Tacrolimus treatment in renal transplant patients in association with genetic variants ofAmerican journal of clinical and experimental urology · 2023Review
- Review
- Tacrolimus troughs and genetic determinants of metabolism in kidney transplant recipients: A comparison of four ancestry groups.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2019Observational
- Attempted validation of 44 reported SNPs associated with tacrolimus troughs in a cohort of kidney allograft recipients.Pharmacogenomics · 2018Article
- IL-3 and CTLA4 gene polymorphisms may influence the tacrolimus dose requirement in Chinese kidney transplant recipients.Acta pharmacologica Sinica · 2017Article
- Influence of IL-18 and IL-10 Polymorphisms on Tacrolimus Elimination in Chinese Lung Transplant Patients.Disease markers · 2017Article
Corrections and comments
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Authors and funding
6 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeInterleukin 18 (IL-18) is a potent proinflammatory cytokine thought to down-regulate cytochrome P450 (CYP) enzyme activities. This study aimed to assess the potential influence of two functional single nucleotide polymorphisms (SNPs) in the IL-18 promoter region on the tacrolimus pharmacokinetics in Chinese renal transplant patients.
methodsWe enrolled 96 renal allograft recipients receiving tacrolimus-based immunosuppressive regiments. Two functional SNPs in the IL-18 gene promoter region at the positions -137G/C (rs187283) and -607A/C (rs1946518) and one SNP (rs776746) of CYP3A5 were genotyped using a Mass ARRAY platform. Tacrolimus daily doses (mg/day) and trough tacrolimus concentration (ng/ml) were continuously recorded for 1 month after transplantation.
resultsThe tacrolimus C/D ratio was significantly associated with the IL-18 rs1946518 gene polymorphism in the first month after transplantation (P = 0.0225). We studied the influence of its polymorphism on tacrolimus C/D ratios in subjects with different CYP3A5 genotype backgrounds, and among patients with CYP3A5 expressers, the difference among the three genotypes was even more striking (P < 0.001). We did not find significant differences in tacrolimus C/D ratios between the IL-18 rs187238 genotypes, either nominally or according to the CYP3A5 genotype. In a simple linear regression model, age, hemoglobin (Hb), CYP3A5 gene polymorphisms, and IL-18 A-607C gene polymorphisms were associated with log-transformed tacrolimus C/D ratios (P < 0.05). In the final multiple linear regression model, CYP3A5 polymorphisms were the most important variant, accounting for 19.5 % of total variation involved in tacrolimus pharmacokinetics.
conclusionOur findings suggest that a combined analysis of CYP3A5 and IL-18 promoter polymorphisms may help clinicians develop individualized tacrolimus treatment, which is based on determining CYP3A5 genotype.
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