title: Multidrug-resistance 1 gene single-nucleotide polymorphisms do not influence long-term graft survival after kidney transplantation.
abstract: BACKGROUND
  The single-nucleotide polymorphisms (SNPs) of the Multidrug resistance 1 (MDR1) gene have been associated with changes in the pharmacokinetics of cyclosporine (CsA) and tacrolimus (FK506). Our aim was investigate the influence of MDR1 SNPs on long-term graft survival in a population of kidney transplant recipients.
  
  
  METHODS
  We retrospectively analyzed 154 patients; they were genotyped for the SNPs C1236T, G2677T/A, and C3435T and evaluated for the influence of those 3 SNPs on CsA or FK506 pharmacokinetics and on long-term graft survival.
  
  
  RESULTS
  Thirty-one patients were wild-type for C1236T, G2677T/A, and C3435T polymorphisms (group A), 76 patients had ≥1 heterozygous mutations (group B), and 47 patients had ≥1 homozygous mutations (group C). CsA-receiving patients in group C needed a significantly higher oral dose than patients in groups B and A (P=.02). No differences in FK506 trough level nor in oral dose taken were observed in FK506-receiving patients. Kaplan-Meier analysis did not show survival differences in the 3 groups, and Cox proportional hazards model confirmed that the MDR1 SNPs did not represent a risk for graft loss.
  
  
  CONCLUSIONS
  Pretransplantation determination of MDR1 SNPs may be helpful to optimize the starting dose of CsA but can not predict long-term graft survival.
authors.affiliation: Basilicata Referral Center for Transplantation Hospital of Matera, Matera, Italy. Electronic address: asaracino@inwind.it.
authors.forename: A
authors.initials: A
authors.lastname: Saracino
authors.affiliation: Nephrology Dialysis and Transplantation Unit, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy.
authors.forename: N
authors.initials: N
authors.lastname: Muscaridola
authors.affiliation: X-Life Metapontum Agrobios, Hospital of Matera, Matera, Italy.
authors.forename: R A
authors.initials: RA
authors.lastname: Cifarelli
authors.affiliation: Nephrology Dialysis and Transplantation Unit, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Stallone
authors.affiliation: Nephrology Dialysis and Transplantation Unit, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Grandaliano
authors.affiliation: Basilicata Referral Center for Transplantation Hospital of Matera, Matera, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Santarsia
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D016572:Cyclosporine / Q000627:therapeutic use; D005260:Female; D006085:Graft Survival / Q000235:genetics*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D016559:Tacrolimus / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D016559:Tacrolimus