title: Effect of the ABCB1 3435C>T polymorphism on tacrolimus concentrations and dosage requirements in liver transplant recipients.
abstract: OBJECTIVE
  The effect of ABCB1 3435C>T on tacrolimus concentrations in liver transplant recipients was studied. Tacrolimus is a substrate for P-glycoprotein, the product of the ABCB1 gene. To determine whether the ABCB1 single-nucleotide polymorphism (SNP) 3435C>T was associated with variation in the tacrolimus concentration:dose ratio (C:D) in 42 liver transplant recipients during three months after transplantation.
  
  
  METHODS
  Forty-two Caucasian patients who underwent an orthotopic liver transplantation from cadaveric donors received a basic immunosuppressive regimen containing tacrolimus and corticosteroids; mycophenolate mofetil was added in 18 cases. The SNP 3435C>T in exon 26 was investigated by MboI restriction-enzyme digestion, leading to the identification of CC, TT, or CT status at nucleotide 3435. Results obtained for the three genotypes were compared for each of three values: daily weight-adjusted tacrolimus dose, blood trough tacrolimus concentration, and C:D.
  
  
  RESULTS
  The wild-type genotype (3435CC) was observed in 10 patients (24%); 23 patients (55%) were heterozygous (3435CT) and 9 patients (21%) were homozygous for the mutation (3435TT). One to three days after liver transplantation, the mean +/- S.D. C:D was significantly higher in subjects homozygous for the mutation compared with subjects with the wild-type allele (236 +/- 119 ng . kg/mL . mg versus 104 +/- 74 ng . kg/mL . mg, respectively; p = 0.0167). Subjects with the heterozygous allele had an intermediate mean +/- S.D. C:D (131 +/- 108 ng . kg/mL . mg). One or three months after transplantation, no significant difference in the tacrolimus C:D was evident among the three groups.
  
  
  CONCLUSIONS
  The ABCB1 3435C>T polymorphism influenced the tacrolimus C:D in the first days after liver transplantation.
authors.affiliation: Pharmacy-Pharmacology Service, Hôpital Paul Brousse, Villejuif, France. laurence.bonhomme-faivre@pbr.aphp.fr
authors.forename: Laurence
authors.initials: L
authors.lastname: Bonhomme-Faivre
authors.forename: Véronique
authors.initials: V
authors.lastname: Picard
authors.forename: Faouzi
authors.initials: F
authors.lastname: Saliba
authors.forename: Chadi
authors.initials: C
authors.lastname: Abbara
authors.forename: Madjid
authors.initials: M
authors.lastname: Fodil
authors.forename: Mélanie
authors.initials: M
authors.lastname: Chaunoy
authors.forename: Robert
authors.initials: R
authors.lastname: Farinotti
mesh_terms: D005260:Female; D005838:Genotype; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D016559:Tacrolimus / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D007166:Immunosuppressive Agents; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D016559:Tacrolimus; C421109:multidrug resistance-associated protein 1