Influence of IL-18 and IL-10 Polymorphisms on Tacrolimus Elimination in Chinese Lung Transplant Patients

Dis Markers. 2017:2017:7834035. doi: 10.1155/2017/7834035. Epub 2017 Jan 26.

Abstract

Aims. The influence of interleukin-10 (IL-10) and interleukin-18 (IL-18) polymorphisms on tacrolimus pharmacokinetics had been described in liver and kidney transplantation. The expression of cytokines varied in different kinds of transplantation. The influence of IL-10 and IL-18 genetic polymorphisms on the pharmacokinetic parameters of tacrolimus remains unclear in lung transplantation. Methods. 51 lung transplant patients at Shanghai Pulmonary Hospital were included. IL-18 polymorphisms (rs5744247 and rs1946518), IL-10 polymorphisms (rs1800896, rs1800872, and rs3021097), and CYP3A5 rs776746 were genotyped. Dose-adjusted trough blood concentrations (C/D ratio, mg/kg body weight) in lung transplant patients during the first 4 postoperative weeks were calculated. Results. IL-18 rs5744247 allele C and rs1946518 allele A were associated with fast tacrolimus metabolism. Combined analysis showed that the numbers of low IL-18 mRNA expression alleles had positive correlation with tacrolimus C/D ratios in lung transplant recipients. The influence of IL-18 polymorphisms on tacrolimus C/D ratios was observed in CYP3A5 expresser recipients, but not in CYP3A5 nonexpresser recipients. No clinical significance of tacrolimus C/D ratios difference of IL-10 polymorphisms was found in our data. Conclusions. IL-18 polymorphisms may influence tacrolimus elimination in lung transplantation patients.

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Asian People
  • Cytochrome P-450 CYP3A / genetics*
  • Cytochrome P-450 CYP3A / immunology
  • Female
  • Gene Expression
  • Genotype
  • Humans
  • Immunosuppressive Agents / blood*
  • Immunosuppressive Agents / pharmacokinetics
  • Immunosuppressive Agents / therapeutic use
  • Inactivation, Metabolic
  • Interleukin-10 / genetics*
  • Interleukin-10 / immunology
  • Interleukin-18 / genetics*
  • Interleukin-18 / immunology
  • Lung Transplantation*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • RNA, Messenger / genetics*
  • RNA, Messenger / immunology
  • Tacrolimus / blood*
  • Tacrolimus / pharmacokinetics
  • Tacrolimus / therapeutic use

Substances

  • IL10 protein, human
  • Immunosuppressive Agents
  • Interleukin-18
  • RNA, Messenger
  • Interleukin-10
  • CYP3A5 protein, human
  • Cytochrome P-450 CYP3A
  • Tacrolimus