title: Effects of Genetic Polymorphism in CYP3A4 and CYP3A5 Genes on Tacrolimus Dose Among Kidney Transplant Recipients.
abstract: BACKGROUND
  This study aimed to evaluate the effects of single nucleotide polymorphisms CYP3A4*1B and CYP3A5*3 on tacrolimus dose requirement among kidney transplant recipients.
  
  
  METHODS
  Blood levels of tacrolimus were measured using microparticle enzyme immunoassay. Genotyping analysis utilized specific polymerase chain reaction-restriction fragment length polymorphism methods for 137 kidney transplant recipients.
  
  
  RESULTS
  The median tacrolimus dose was significantly lower in the CYP3A4*1/*1 carriers (0.06 mg/kg/d; range, 0.007 mg/kg/d to 0.17 mg/kg/d) as compared to the CYP3A4*1B/*1B carriers (0.1 mg/kg/d; range, 0.03 mg/kg/d to 0.22 mg/kg/d; P = .001). Patients with at least 1 CYP3A5*1 wild-type allele required higher median doses of tacrolimus (median, 0.08 mg/kg/d; range, 0.03 mg/kg/d to 0.22 mg/kg/d) as compared to the CYP3A5*3 carriers (median, 0.05 mg/kg/d; range, 0.007 mg/kg/d  to 0.17 mg/kg/d; P = .002).
  
  
  CONCLUSIONS
  This study showed that tacrolimus dose requirement is lower in Jordanian kidney transplant recipients compared to other populations. Moreover, we found a correlation between genetic variations in CYP3A4 and CYP3A5 enzymes and tacrolimus blood levels among our kidney transplant recipients.
authors.affiliation: Department of Biopharmaceutics and Clinical Pharmacy, College of Pharmacy, University of Jordan, Amman, Jordan. ayousef@ju.edu.jo.
authors.forename: Al-Motassem
authors.initials: AM
authors.lastname: Yousef
authors.forename: Hisham
authors.initials: H
authors.lastname: Qosa
authors.forename: Nailya
authors.initials: N
authors.lastname: Bulatova
authors.forename: Ali
authors.initials: A
authors.lastname: Abuhaliema
authors.forename: Hussein
authors.initials: H
authors.lastname: Almadhoun
authors.forename: Ghada
authors.initials: G
authors.lastname: Khayyat
authors.forename: Muhammad
authors.initials: M
authors.lastname: Olemat
mesh_terms: D000328:Adult; D065095:Calcineurin Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D007597:Jordan / Q000208:ethnology; D016030:Kidney Transplantation; D008297:Male; D012150:Polymorphism, Restriction Fragment Length / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D016559:Tacrolimus / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D066027:Transplant Recipients
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D016559:Tacrolimus