title: Functional G1199A ABCB1 polymorphism may have an effect on cyclosporine blood concentration in renal transplanted patients.
abstract: Cyclosporine A (CsA) shows significant inter-individual variability in its pharmacokinetics, which may be due to polymorphisms in ABCB-1 genes coding for P-glycoprotein. The aim of this study was to explore the role of genetic polymorphisms of ABCB-1 in affecting the CsA blood concentrations in renal transplanted patients over the first 3 months after transplantation. Renal transplanted patients receiving CsA (n = 40) were genotyped for ABCB -1 C3435T (I1145I) and G1199A (S400N) polymorphisms. CsA blood concentrations were measured on Day 7, 30, and 90 after transplantation. G1199A variant showed higher CsA blood concentrations in stable patients, that was significant for trough levels (198 vs. 136 ng/mL on Day 7, P = .004, 196 vs. 125 ng/mL on Day 30, P = .007, 194 vs. 121 ng/mL on Day 90, P = .005 for stable vs. unstable groups). Polymorphisms of ABCB-1 have only a minor effect on CsA blood concentrations. The functional G1199A polymorphism can affect the drug levels more than non-functional C3435T. This polymorphism might be of a potential prognostic value in renal transplanted patients.
authors.affiliation: College of Medicine, Beni-Suif University, Beni-Suif, Egypt.
authors.forename: Gomaa
authors.initials: G
authors.lastname: Mostafa-Hedeab
authors.forename: Maha M
authors.initials: MM
authors.lastname: Saber-Ayad
authors.forename: Inas A
authors.initials: IA
authors.lastname: Latif
authors.forename: Sahier O
authors.initials: SO
authors.lastname: Elkashab
authors.forename: Tarek H
authors.initials: TH
authors.lastname: Elshaboney
authors.forename: Magdy Ibrahim
authors.initials: MI
authors.lastname: Mostafa
authors.forename: Sanaa Abd
authors.initials: SA
authors.lastname: El-Shafy
authors.forename: Magda M
authors.initials: MM
authors.lastname: Zaki
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D016572:Cyclosporine / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000493:pharmacokinetics*; D016030:Kidney Transplantation; D008297:Male; D020641:Polymorphism, Single Nucleotide
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D007166:Immunosuppressive Agents; D016572:Cyclosporine
keywords: MDR-1 gene polymorphisms; cyclosporine; p-glycoprotein; pharmacogenetics; renal transplantation