title: Effect of MDR1 polymorphisms on the blood concentrations of tacrolimus in Turkish renal transplant patients.
abstract: BACKGROUND
  Tacrolimus, a calcineurin inhibitör, is prescribed to prevent allograft rejection in renal transplantation. Tacrolimus not only has a narrow therapeutic index, but also shows significant interindividual differences. The absorption and metabolism of this drug are affected by multidrug resistance (MDR) 1 gene polymorphisms that correlated with single-nucleotide polymorphisms (SNPs) affecting in vivo P-glycoprotein activity. This study investigated associations of MDR1 gene C3435T polymorphism with tacrolimus blood concentrations and dose requirements as well as acute rejection episodes among Turkish renal transplant patients.
  
  
  METHODS
  One hundred living-donor transplant recipients and 150 healthy control subjects underwent C3435T genotyping using polymerase chain reaction-restriction fragment length polymorphism. Blood concentrations of tacrolimus were determined with the cloned enzyme donor immunoassay.
  
  
  RESULTS
  The CC, CT, and TT genotype frequencies among patients were, respectively, 44.0%, 33.0%, and 23.0% versus 36.7%, 43.3%, and 20.0% among control subjects. There was no significant difference between (P = .061; P = .102; P = .211; respectively). The ratio of blood concentration to dose of tacrolimus for patients with mutant homozygous 3435 TT genotype was higher than that of wild-type 3435 CC genotype homozygous individuals. The doses for these patients were lower at 1, 3, and 12 months (P = .048; P = .03; P = .041, respectively). There were no significant differences between the groups regarding coprescription of drugs that affect tacrolimus concentrations, such as diltiazem. Acute rejection episodes were not associated with the CC vs CT or TT genotypes: odds ratio (OR), 0.517 (95% confidence interval [CI], 0.190-1.407; P = .192); OR 1.558 (95% CI, 0.587-4.136; P = .372); OR 1.346; (95% CI, 0.456-3.968; P = .590), respectively.
  
  
  CONCLUSIONS
  Determination of MDR1 polymorphism may help to achieve target of tacrolimus blood concentrations.
authors.affiliation: Medical Biology Department, Istanbul Medicine Faculty, Istanbul University, Capa, Istanbul, Turkey. hayriyesenturk@gmail.com
authors.forename: H S
authors.initials: HS
authors.lastname: Ciftci
authors.forename: T K
authors.initials: TK
authors.lastname: Ayna
authors.forename: Y K
authors.initials: YK
authors.lastname: Caliskan
authors.forename: I
authors.initials: I
authors.lastname: Guney
authors.forename: H
authors.initials: H
authors.lastname: Bakkaloglu
authors.forename: I
authors.initials: I
authors.lastname: Nane
authors.forename: A E
authors.initials: AE
authors.lastname: Aydin
authors.forename: A
authors.initials: A
authors.lastname: Turkmen
authors.forename: M
authors.initials: M
authors.lastname: Gurtekin
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000328:Adult; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood* / Q000627:therapeutic use; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D016559:Tacrolimus / Q000097:blood* / Q000627:therapeutic use; D014421:Turkey; D055815:Young Adult
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D007166:Immunosuppressive Agents; D016559:Tacrolimus