title: The influence of the tumor necrosis factor-alpa-308G>A polymorphism on the efficacy of immunosuppressive therapy in patients after kidney transplantation.
abstract: Cytokines play an important role in the immune response. The calcineurin inhibitors (cyclosporine CsA, tacrolimus TAC) widely used after renal transplantation to prevent allograft rejection are immunosuppressive drugs suppressing the production of cytokines. These drugs are characterized by interindividual variability and require monitoring their blood concentrations to predict their optimal dosage. Therefore, the aim of the study was to determine the correlation between therapeutic effects of immunosuppressants and the tumor necrosis factor-α (TNF-α)-308G>A polymorphism in renal transplant patients. A total of 412 patients receiving TAC and CsA were included in the study. Genotype frequencies were determined using the real-time PCR method. Patients with the GG genotype received higher doses of TAC as compared to carriers of the GA genotype (5.24 mg versus 3.35 mg) and had lower mean drug concentration in blood (5.86 ng/ml versus 6.92 ng/ml). Similar results were also obtained for CsA (GG: 185.33 mg versus GA: 153.30 mg, P < 0.05). The comparison of the TNF-α-308G>A polymorphism with the biochemical parameters did not reveal a potential risk for transplant rejection. These results indicate that the TNF-α-308G>A polymorphism may influence the dosage of immunosuppressive drugs in patients after transplantation as far as individualization of drug therapy is concerned.
authors.affiliation: Department of General Pathology, Pomeranian Medical University, Szczecin, Poland. maciej.j.kotowski@gmail.com.|Department of General Surgery and Transplantation, Pomeranian Medical University, Szczecin, Poland.
authors.forename: M
authors.initials: M
authors.lastname: M Kotowski
authors.affiliation: Department of Stem Cells and Regenerative Medicine, Institute of Natural Fibres and Medicinal Plants, Poznan, Poland.|Department of Histocompatibility with Laboratory of Genetic Diagnostics, Regional Blood Center, Poznan, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Bogacz
authors.affiliation: Laboratory of Experimental Pharmacogenetics, Department of Clinical Pharmacy and Biopharmacy, University of Medical Sciences, Poznan, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Bartkowiak-Wieczorek
authors.affiliation: Department of General Surgery and Transplantation, Pomeranian Medical University, Szczecin, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Sienko
authors.affiliation: Department of Laboratory Diagnostics, Greater Poland Cancer Centre, Poznan, Poland.
authors.forename: D
authors.initials: D
authors.lastname: Procyk
authors.affiliation: Nephrology-Transplant Center, Department of the Regional Public Hospital in Szczecin, Szczecin, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Dziewanowski
authors.affiliation: Department of General Surgery and Transplantation, Pomeranian Medical University, Szczecin, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Ostrowski
authors.affiliation: Department of Stem Cells and Regenerative Medicine, Institute of Natural Fibres and Medicinal Plants, Poznan, Poland.|Department of General Pharmacology and Pharmacoeconomics, Pomeranian Medical University, Szczecin, Poland.
authors.forename: B
authors.initials: B
authors.lastname: Czerny
authors.affiliation: Laboratory of Experimental Pharmacogenetics, Department of Clinical Pharmacy and Biopharmacy, University of Medical Sciences, Poznan, Poland.
authors.forename: E
authors.initials: E
authors.lastname: Grzeskowiak
authors.affiliation: Department of General Pathology, Pomeranian Medical University, Szczecin, Poland.
authors.forename: B
authors.initials: B
authors.lastname: Machalinski
mesh_terms: D016572:Cyclosporine / Q000008:administration & dosage; D016207:Cytokines / Q000235:genetics; D005838:Genotype; D006084:Graft Rejection / Q000097:blood / Q000188:drug therapy* / Q000235:genetics*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D016030:Kidney Transplantation / Q000009:adverse effects; D011110:Polymorphism, Genetic / Q000235:genetics*; D016559:Tacrolimus / Q000008:administration & dosage; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D016207:Cytokines; D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha; D016572:Cyclosporine; D016559:Tacrolimus