In:
Pharmacogenomics, Future Medicine Ltd, Vol. 20, No. 6 ( 2019-04), p. 447-456
Kurzfassung:
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 IL-17R (p 〈 0.01), while IL-17 recombinant protein had no influence on the expressions of CYP3A4 and CYP3A5 when PXR was downregulated. Conclusion: This study revealed the possible association of IL-17 G-197A with cyclosporine metabolism and transplant rejection after LT, which might be partly related to the upregulations of CYP3A4/5 dependent on PXR.
Materialart:
Online-Ressource
ISSN:
1462-2416
,
1744-8042
DOI:
10.2217/pgs-2018-0198
Sprache:
Englisch
Verlag:
Future Medicine Ltd
Publikationsdatum:
2019
SSG:
15,3
