title: Donor IL-18 rs5744247 polymorphism as a new biomarker of tacrolimus elimination in Chinese liver transplant patients during the early post-transplantation period: results from two cohort studies.
abstract: OBJECTIVE
  This study evaluated the relationships between IL-18 polymorphisms and tacrolimus elimination in Chinese liver transplant patients.
  
  
  METHODS
  Eighty-four liver transplant patients from Shanghai (training set) and 50 patients from Shandong (validating set) were inculded. IL-18 polymorphisms (rs5744247, rs7106524, rs549908, rs187238 and rs1946518) and CYP3A5 rs776746 were genotyped.
  
  
  RESULTS
  In training set, daily drug dose, total bilirubin, donor CYP3A5 rs776746 and IL-18 rs5744247 genotypes were screened to construct prediction model for tacrolimus elimination. This model was confirmed in validating set (p < 0.001). Donor IL-18 rs5744247 polymorphism was an independent predictor of tacrolimus elimination in the first week after transplantation in both training (p = 0.008) and validating cohorts (p = 0.033).
  
  
  CONCLUSIONS
  Donor IL-18 rs5744247 polymorphism may influence on tacrolimus elimination. Original submitted 16 July 2014; Revision submitted 12 November 2014.
authors.affiliation: Department of General Surgery, Shanghai First People's Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Junwei
authors.initials: J
authors.lastname: Fan
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Zhang
authors.forename: Lei
authors.initials: L
authors.lastname: Ren
authors.forename: Dawei
authors.initials: D
authors.lastname: Chen
authors.forename: Shaohan
authors.initials: S
authors.lastname: Wu
authors.forename: Feng
authors.initials: F
authors.lastname: Guo
authors.forename: Shengying
authors.initials: S
authors.lastname: Qin
authors.forename: Zhaowen
authors.initials: Z
authors.lastname: Wang
authors.forename: Zhong
authors.initials: Z
authors.lastname: Lin
authors.forename: Tonghai
authors.initials: T
authors.lastname: Xing
authors.forename: Xing
authors.initials: X
authors.lastname: Sun
authors.forename: Zhihai
authors.initials: Z
authors.lastname: Peng
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics*; D002681:China; D015331:Cohort Studies; D051544:Cytochrome P-450 CYP3A / Q000235:genetics; D016903:Drug Monitoring; D005260:Female; D005786:Gene Expression Regulation; D005787:Gene Frequency; D005819:Genetic Markers; D056945:Hep G2 Cells; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D020382:Interleukin-18 / Q000235:genetics* / Q000378:metabolism; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016559:Tacrolimus / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D014019:Tissue Donors; D055815:Young Adult
chemical_list: D005819:Genetic Markers; C000589760:IL18 protein, human; D007166:Immunosuppressive Agents; D020382:Interleukin-18; D012333:RNA, Messenger; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; D016559:Tacrolimus
keywords: CYP3A5; IL-18; SNP; liver transplantation; tacrolimus