title: Association of CYP3A4*18B and CYP3A5*3 polymorphism with cyclosporine-related liver injury in Chinese renal transplant recipients.
abstract: OBJECTIVE
  The purpose of this study was to investigate the associations between CYP3A4*18B and CYP3A5*3 polymorphism and cyclosporine-related liver injuries in Chinese renal transplant recipients.
  
  
  METHODS
  We genotyped 339 renal transplant recipients treated with a triple immunosuppressive regimen including cyclosporine for CYP3A4*18B and CYP3A5*3 polymorphism using the polymerase chain reaction restriction fragment length polymorphism assay.
  
  
  RESULTS
  The incidence of liver injury in the study population was 36.9% (125/339). At 1 month after transplantation, the trough concentration of cyclosporine (C0) in the group with CYP3A4*1/*1(GG alleles) was significantly higher than in the group with CYP3A4*18B/*1 8B(AA alleles) (p < 0.05). At 3 months after transplantation, the C0 in the group with CYP3A4*1/*1 and group with CYP3A4*1/*18B was markedly higher than in the group with CYP3A4*18B/*18B (p < 0.05). The GG genotypes of CYP3A4*18B were more common in the liver injury group compared with the control group (p < 0.05). Univariate logistic regression analysis showed that subjects carrying the GG genotypes had a 5.136- and 2.528-fold higher risk of developing cyclosporine-related liver injury than those with the AA and GA genotypes. When adjusted for sex, the risk of the CYP3A4*18B genotypes was OR = 4.969 for GG compared to AA (p = 0.030), and OR = 2.634 for GG compared to GA (p = 0.025). However, no association was observed between CYP3A5*3 polymorphisms with cyclosporine-related liver injury.
  
  
  CONCLUSIONS
  These results suggested that the wild type of CYP3A4*18B is a risk factor for the development of cyclosporine- related liver injuries in Chinese renal transplant recipients.
authors.forename: Hua-wen
authors.initials: HW
authors.lastname: Xin
authors.forename: Hui-ming
authors.initials: HM
authors.lastname: Liu
authors.forename: Yuan-qi
authors.initials: YQ
authors.lastname: Li
authors.forename: Hui
authors.initials: H
authors.lastname: Huang
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Ai-rong
authors.initials: AR
authors.lastname: Yu
authors.forename: Xiao-chun
authors.initials: XC
authors.lastname: Wu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics*; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology / Q000208:ethnology / Q000209:etiology* / Q000235:genetics; D016009:Chi-Square Distribution; D002681:China / Q000453:epidemiology; D016572:Cyclosporine / Q000009:adverse effects* / Q000097:blood; D051544:Cytochrome P-450 CYP3A / Q000235:genetics* / Q000378:metabolism; D004359:Drug Therapy, Combination; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000097:blood; D015994:Incidence; D016030:Kidney Transplantation / Q000009:adverse effects; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D012307:Risk Factors; D013997:Time Factors; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human