title: Impact of interleukin-10 gene polymorphisms on tacrolimus dosing requirements in Chinese liver transplant patients during the early posttransplantation period.
abstract: OBJECTIVE
  Pharmacogenetics holds the potential to elucidate the inherited basis of differences between individual responses to drugs. Impacts of CYP3A5 and ABCB1 gene polymorphisms on the immunosuppressant tacrolimus have been reported in previous studies of liver transplantation. The functions of interleukin-10 (IL-10) gene expression are complex in the early period after liver transplantation. In this study, we examined the IL-10 genotypes of both recipients and donors to clarify the influence of these genetic variants on tacrolimus dose requirements and pharmacokinetics.
  
  
  METHODS
  Genetic polymorphisms of IL-10, CYP3A5, and ABCB1 were evaluated for 53 liver transplant recipients and 53 donors. Tacrolimus doses and blood concentrations were determined at 1, 2, and 3 weeks, and 1 month after transplantation. IL-10 polymorphisms at G-1082A, C-819 T, and C-592A; CYP3A5 polymorphisms at A6986G; and ABCB1 polymorphisms at C1236T, G2677T, and C3435T were assessed by PCR amplification and DNA sequencing.
  
  
  RESULTS
  Recipients who received organs from CYP3A5*3/*3 donors had higher tacrolimus C/D ratios. In the first 2 weeks, the tacrolimus C/D ratios of the recipients with donors who were CYP3A5 nonexpressors and had a low IL-10 production genotype (-819TT, -592 AA) were higher than those with donors who were CYP3A5 nonexpressors and had a high IL-10 production genotype (-819CC or CT, -592CC or AC). There were no significant differences in laboratory data or clinical characteristics (which could influence the tacrolimus C/D ratio) between the two groups of patients (P > 0.05).
  
  
  CONCLUSIONS
  Determining IL-10 and CYP3A5 polymorphisms of donors may allow individualized tacrolimus dosage regimens to be determined for liver transplant patients during the early posttransplantation period.
authors.affiliation: Department of Pharmacy, Shanghai First People's Hospital, Shanghai Jiaotong University, Shanghai, 200080, China.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Zhang
authors.forename: Zhaowen
authors.initials: Z
authors.lastname: Wang
authors.forename: Junwei
authors.initials: J
authors.lastname: Fan
authors.forename: Gaolin
authors.initials: G
authors.lastname: Liu
authors.forename: Zhihai
authors.initials: Z
authors.lastname: Peng
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000328:Adult; D002681:China; D051544:Cytochrome P-450 CYP3A / Q000235:genetics; D016903:Drug Monitoring; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D016753:Interleukin-10 / Q000235:genetics* / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011184:Postoperative Period; D012189:Retrospective Studies; D016559:Tacrolimus / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D014019:Tissue Donors; D055815:Young Adult
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; C508609:IL10 protein, human; D007166:Immunosuppressive Agents; D016753:Interleukin-10; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; D016559:Tacrolimus