The interleukin-17 G-197A polymorphism is associated with cyclosporine metabolism and transplant rejection in liver transplant recipients

Pharmacogenomics
Bo SunGaolin Liu

Abstract

Aim: This study aimed to investigate the effect of and mechanism involved in the IL-17 SNP on cyclosporine metabolism and outcomes of liver transplantation (LT). Materials & methods: The IL-17 genotype, IL-17 expression, postoperative outcome and cyclosporine concentration were reviewed in 106 LT recipients. The functional relevance of rs2275913 was evaluated by luciferase assay. Furthermore, L02 cells were treated with IL-17 recombinant protein or/and pregnane X receptor (PXR) knockdown lentiviruses, then the expression of PXR, CYP3A4, CYP3A5 and IL-17R were detected by PCR and western blotting. Result: The significant distribution difference at IL-17 locus G-197A was confirmed between patients with and without rejection (p = 0.035). Patients with acute rejection showed higher IL-17 level than those without rejection. Cyclosporine concentration was associated with the different IL-17 genotype (p < 0.05). Luciferase assay revealed that 197G genotype had higher luciferase activity than that in 197A genotype (p = 0.009). Furthermore, IL-17 recombinant protein remarkably promoted the expressions of PXR, CYP3A4 and CYP3A5 (p < 0.01), but not IL-17R. PXR knockdown significantly inhibited the mRNA levels of CYP3A4 and CYP3A5 but not ...Continue Reading

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Citations

Aug 4, 2020·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Pingyun YuanYan Jin
Jun 9, 2020·Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society·Taisa J KohutBrendan J Keating
Apr 8, 2020·World Journal of Gastroenterology : WJG·Tomislav KelavaAnna Mrzljak

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Methods Mentioned

BETA
ELISA
PCR
Assay
enzyme linked-immunosorbent assay

Software Mentioned

SPSS

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