title: A search for cyclophilin-A gene variants in cyclosporine A-treated renal transplanted patients.
abstract: BACKGROUND
  The cyclophilin A (CypA)-cyclosporine (CsA) complex promotes immune response. The variation at the CypA gene could explain CsA-pharmacokinetics and clinical outcomes among CsA-treated patients.
  
  
  METHODS
  The study included 290 kidney transplanted patients (65% male; mean age 51 +/- 15 yr), treated with CsA. The five CypA- exons and the promoter region were analysed through single-strand conformation analysis, denaturing high performance liquid chromatography, and direct sequencing. The effect of a promoter polymorphism (-11 G/C) on gene expression was analysed in cell-cultures.
  
  
  RESULTS
  We found two polymorphisms in the promoter (-11 G/C) and exon 1 (+36 G/A). Genotype frequencies did not differ between patients according to their pharmacokinetics status. In vitro studies showed that -11 G/C affected gene expression. The -11 G allele was significantly associated with clinical nephrotoxicity (p = 0.006). The strongest predictors for nephrotoxicity were a donor age > or =55 yr, and the promoter GG + GC genotypes.
  
  
  CONCLUSIONS
  Our work suggests that a CypA-promoter polymorphism (-11 G/C) could be associated with clinical nephrotoxicity. Replication of this study in other populations is necessary to define the role of CypA-variants in the main clinical outcomes among CsA-treated kidney-transplanted patients.
authors.affiliation: Servicio de Nefrología-Hospital Central de Asturias, Oviedo, Spain.
authors.forename: Grace Tamara
authors.initials: GT
authors.lastname: Moscoso-Solorzano
authors.forename: Francisco
authors.initials: F
authors.lastname: Ortega
authors.forename: Isabel
authors.initials: I
authors.lastname: Rodríguez
authors.forename: Mónica
authors.initials: M
authors.lastname: García-Castro
authors.forename: Ernesto
authors.initials: E
authors.lastname: Gómez
authors.forename: Carmen
authors.initials: C
authors.lastname: Díaz-Corte
authors.forename: José M
authors.initials: JM
authors.lastname: Baltar
authors.forename: Victoria
authors.initials: V
authors.lastname: Alvarez
authors.forename: Alberto
authors.initials: A
authors.lastname: Ortiz
authors.forename: Eliecer
authors.initials: E
authors.lastname: Coto
mesh_terms: D000328:Adult; D002851:Chromatography, High Pressure Liquid; D021984:Cyclophilin A / Q000235:genetics*; D016572:Cyclosporine / Q000627:therapeutic use*; D005260:Female; D005838:Genotype; D006085:Graft Survival / Q000187:drug effects* / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational; D011401:Promoter Regions, Genetic / Q000235:genetics
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D021984:Cyclophilin A