title: Influence of cytochrome P450 3A5 polymorphisms on viral infection incidence in kidney transplant patients treated with tacrolimus.
abstract: OBJECTIVE
  The aim of this retrospective study was to determine the risk of viral infection in tacrolimus-treated kidney transplant patients.
  
  
  METHODS
  We analyzed kidney transplant recipients from 2002 to 2012, reporting all episodes of viral infection. All patients received induction with basiliximab followed by a standard regimen with tacrolimus, steroids, and antimetabolites. Genotypes of cytochrome P450 (CYP) 3A5 were determined with the use of the polymerase chain reaction method.
  
  
  RESULTS
  Fifty-one patients (17 women, 34 men; mean age, 41.6 ± 65.7 years) underwent kidney transplantation with tacrolimus-based immunosuppressive therapy. Thirty patients were diagnosed with 34 viral infections, including herpes simplex, adenovirus, mumps, varicella, and cytomegalovirus (CMV). CMV was the most common viral infection. In multivariate analysis, the CYP3A5 1 allele (P = .049) and negative serology for CMV (P = .018) were factors independently associated with the incidence of viral infection. After excluding CMV infection in CMV-seropositive donor/CMV-seronegative (D+R-) recipients in the analysis, the presence of the CYP3A5 1 allele was found to be an independent risk factor for viral infection. Recipients with the CYP3A5 3/3 genotype (nonexpressors) showed significantly higher dose-adjusted tacrolimus trough concentrations than patients with the CYP3A5 1 allele (expressors; respectively, 104.6 ± 65.6 vs 52.6 ± 62.3 ng/mL per mg/kg/d).
  
  
  CONCLUSIONS
  The CYP3A5 1 allele is associated with viral infection, possibly as a result of higher peak concentrations of tacrolimus. Further analyses, such as area under the concentration-time curve (AUC) for tacrolimus and polymorphisms of drug metabolism enzymes such as CYP3A4 are required to evaluate the influence of CYP3A5 on viral infection in kidney transplantation.
authors.affiliation: Department of Urology and Renal Transplantation, Yokohama City University Medical Center, Yokohama, Japan. Electronic address: hatu98@yokohama-cu.ac.jp.
authors.forename: Y
authors.initials: Y
authors.lastname: Hattori
authors.affiliation: Department of Laboratory Medicine, Yokohama City University Medical Center, Yokohama, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Tanaka
authors.affiliation: Department of Urology and Renal Transplantation, Yokohama City University Medical Center, Yokohama, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Teranishi
authors.affiliation: Department of Urology and Renal Transplantation, Yokohama City University Medical Center, Yokohama, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Ishida
authors.affiliation: Department of Urology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Makiyama
authors.affiliation: Department of Laboratory Medicine, Yokohama City University Medical Center, Yokohama, Japan.
authors.forename: E
authors.initials: E
authors.lastname: Miyajima
authors.affiliation: Department of Urology and Renal Transplantation, Yokohama City University Medical Center, Yokohama, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Noguchi
authors.affiliation: Department of Urology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Kubota
mesh_terms: D000328:Adult; D000368:Aged; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D016559:Tacrolimus / Q000627:therapeutic use*; D014777:Virus Diseases / Q000235:genetics*
chemical_list: D007166:Immunosuppressive Agents; D051544:Cytochrome P-450 CYP3A; D016559:Tacrolimus