ArticlePloS one2013
Novel single nucleotide polymorphisms in interleukin 6 affect tacrolimus metabolism in liver transplant patients.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 20 citations in OpenAlex.
- Association between interleukin-18 promoter variants and tacrolimus pharmacokinetics in Chinese renal transplant patients.European journal of clinical pharmacology · 2015Trial
- Influence of TLR4 rs1927907 locus polymorphisms on tacrolimus pharmacokinetics in the early stage after liver transplantation.European journal of clinical pharmacology · 2014Trial
- Single nucleotide polymorphisms in interleukin-6 attenuates hepatocytes injury in hypoxia/re-oxygenation via STAT3 signal pathway mediated autophagy.Molecular biology reports · 2021Article
- Albumin-bilirubin grade as a prognostic factor of hepatocellular carcinoma after treatment with orthotopic liver transplantation.Translational cancer research · 2019Article
- Attempted validation of 44 reported SNPs associated with tacrolimus troughs in a cohort of kidney allograft recipients.Pharmacogenomics · 2018Article
- Translational medical research and liver transplantation: systematic review.Translational gastroenterology and hepatology · 2018Review
- Gene Variations of Sixth Complement Component Affecting Tacrolimus Metabolism in Patients with Liver Transplantation for Hepatocellular Carcinoma.Chinese medical journal · 2017Article
- Interleukin-6 and rs1800796 locus single nucleotide polymorphisms in response to hypoxia/reoxygenation in hepatocytes.International journal of molecular medicine · 2016Article
- Tacrolimus in preventing transplant rejection in Chinese patients--optimizing use.Drug design, development and therapy · 2015Review
- Article
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Corrections and comments
- Retraction · 2019-09-04Ethical Violations by Author · Informed/Patient Consent - None/Withdrawn · Investigation by Journal/Publisher · Lack of IRB/IACUC Approval and/or Compliance ·
- Retracted
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTacrolimus is the first-line immunosuppressant after organ transplantation. It is mainly metabolized by cytochrome P450, family 3, subfamily A (CYP3A) enzymes, but there are large individual differences in metabolism. Interleukin 6 (IL6) has been shown to cause a pan-suppression of mRNA levels of ten major CYP enzymes in human hepatocyte cultures. IL6 has been shown to provide hepatoprotection in various models of liver injury. Rs1800796 is a locus in the IL6 gene promoter region which regulates cytokine production. We speculated that IL6 rs1800796 polymorphisms may lead to individual differences in tacrolimus metabolism by affecting CYP3A enzymes levels and liver function after liver transplantation. METHODOLOGY/PRINCIPAL
findingsNinety-six liver transplant patients receiving tacrolimus were enrolled in the study. Two single nucleotide polymorphisms (SNP), CYP3A5 rs776746 and IL6 rs1800796, were genotyped in both donors and recipients. The effects of SNPs on tacrolimus concentration/dose (C/D ratio) at four weeks after transplantation were studied, as well as the effects of donor IL6 rs1800796 polymorphisms on liver function. Both donor and recipient CYP3A5 rs776746 allele A showed association with lower C/D ratios, while donor IL6 rs1800796 allele G showed an association with higher C/D ratios. Donor CYP3A5 rs776746 allele A, IL6 rs1800796 allele C, and recipient CYP3A5 rs776746 allele A were associated with fast tacrolimus metabolism. With increasing numbers of these alleles, patients were found to have increasingly lower tacrolimus C/D ratios at time points after transplantation. Donor IL6 rs1800796 allele G carriers showed an association with higher glutamic-pyruvic transaminase (GPT) levels.
conclusionsCombined analysis of donor CYP3A5 rs776746, IL6 rs1800796, and recipient CYP3A5 rs776746 polymorphisms may distinguish tacrolimus metabolism better than CYP3A5 rs776746 alone. IL6 may lead to individual differences in tacrolimus metabolism mainly by affecting liver function.
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