title: Influence of IL-18 and IL-10 Polymorphisms on Tacrolimus Elimination in Chinese Lung Transplant Patients.
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-18polymorphisms (rs5744247 and rs1946518), IL-10 polymorphisms (rs1800896, rs1800872, and rs3021097), andCYP3A5rs776746 were genotyped. Dose-adjusted trough blood concentrations (C/Dratio, 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 tacrolimusC/Dratios in lung transplant recipients. The influence of IL-18 polymorphisms on tacrolimusC/Dratios was observed in CYP3A5 expresser recipients, but not in CYP3A5 nonexpresser recipients. No clinical significance of tacrolimusC/Dratios difference of IL-10 polymorphisms was found in our data.Conclusions. IL-18polymorphisms may influence tacrolimus elimination in lung transplantation patients.
authors.affiliation: Department of Pharmacy, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, Jiangwan Hospital of Shanghai Hongkou District, Shanghai, China.
authors.forename: Jiandong
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of General Surgery, Shanghai First People's Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Junwei
authors.identifier: 0000-0001-8214-2974
authors.initials: J
authors.lastname: Fan
authors.affiliation: Department of General Surgery, Shanghai First People's Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Yuping
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Boxiong
authors.initials: B
authors.lastname: Xie
authors.affiliation: Department of Pharmacy, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, Shanghai First People's Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Shengtao
authors.initials: S
authors.lastname: Lin
authors.affiliation: Department of General Surgery, Shanghai First People's Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Ye
authors.affiliation: Department of General Surgery, Shanghai First People's Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Gening
authors.identifier: 0000-0003-0486-014X
authors.initials: G
authors.lastname: Jiang
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D044466:Asian People; D051544:Cytochrome P-450 CYP3A / Q000235:genetics* / Q000276:immunology; D005260:Female; D015870:Gene Expression; D005838:Genotype; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D008658:Inactivation, Metabolic; D016753:Interleukin-10 / Q000235:genetics* / Q000276:immunology; D020382:Interleukin-18 / Q000235:genetics* / Q000276:immunology; D016040:Lung Transplantation; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000235:genetics* / Q000276:immunology; D016559:Tacrolimus / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: C508609:IL10 protein, human; D007166:Immunosuppressive Agents; D020382:Interleukin-18; D012333:RNA, Messenger; D016753:Interleukin-10; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; D016559:Tacrolimus