Donor P-gp polymorphisms strongly influence renal function and graft loss in a cohort of renal transplant recipients on cyclosporine therapy in a long-term follow-up.: Donor's P-gp polymorphisms and graft loss
| العنوان: | Donor P-gp polymorphisms strongly influence renal function and graft loss in a cohort of renal transplant recipients on cyclosporine therapy in a long-term follow-up.: Donor's P-gp polymorphisms and graft loss |
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| المؤلفون: | Pierre Marquet, Eliza Munteanu, Mireille Drouet, Jean-Baptiste Woillard, Marie Essig, Annick Rousseau, Nicolas Picard, J.P. Rerolle, Y. Le Meur, Angélique Guillaudeau |
| المساهمون: | Pharmacologie des Immunosuppresseurs et de la Transplantation (PIST), Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Néphrologie, Dialyse, Transplantations [CHU Limoges], CHU Limoges, Service de Pharmacologie, toxicologie et pharmacovigilance [CHU Limoges], Service d'Hématologie biologique [CHU Limoges], Service d'Immunologie et immunogénétique [CHU Limoges], Service de Néphrologie, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ) |
| المصدر: | Clinical Pharmacology and Therapeutics Clinical Pharmacology and Therapeutics, American Society for Clinical Pharmacology and Therapeutics, 2010, 88 (1), pp.95-100. ⟨10.1038/clpt.2010.62⟩ |
| بيانات النشر: | Nature Pub. Group, 2010. |
| سنة النشر: | 2010 |
| مصطلحات موضوعية: | Graft Rejection, Male, MESH: Tissue Donors, Kaplan-Meier Estimate, Kidney, Kidney Function Tests, MESH: Cyclosporine, 030226 pharmacology & pharmacy, Gastroenterology, MESH: Kidney Transplantation, MESH: Genotype, Cohort Studies, 0302 clinical medicine, MESH: Risk Factors, Risk Factors, Cyclosporin a, Cytochrome P-450 CYP3A, Pharmacology (medical), MESH: Kaplan-Meiers Estimate, MESH: Cohort Studies, Kidney transplantation, pharmacogenetics, MESH: Aged, MESH: Cytochrome P-450 CYP3A, 0303 health sciences, MESH: Middle Aged, Hazard ratio, MESH: Follow-Up Studies, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Middle Aged, Tissue Donors, 3. Good health, medicine.anatomical_structure, MESH: Kidney Function Tests, MESH: Young Adult, Cyclosporine, Female, MESH: Immunosuppressive Agents, Immunosuppressive Agents, medicine.drug, Adult, medicine.medical_specialty, MESH: P-Glycoprotein, ATP Binding Cassette Transporter, Subfamily B, CYP3As, Genotype, Renal function, MESH: Graft Rejection, P-glycoprotein, Article, 03 medical and health sciences, Young Adult, MESH: Analysis of Variance, Internal medicine, MESH: Polymorphism, Genetic, medicine, Humans, ATP Binding Cassette Transporter, Subfamily B, Member 1, graft loss, 030304 developmental biology, Aged, Retrospective Studies, Pharmacology, Analysis of Variance, MESH: Humans, Polymorphism, Genetic, business.industry, MESH: Adult, MESH: Retrospective Studies, Retrospective cohort study, MESH: Haplotypes, MESH: Kidney, Ciclosporin, medicine.disease, Kidney Transplantation, MESH: Male, Surgery, Calcineurin, Haplotypes, business, MESH: Female, cyclosporine A, Follow-Up Studies |
| الوصف: | International audience; Cyclosporin A (CsA) is a substrate for cytochrome P450 3A and the efflux transporter P-glycoprotein (P-gp; ABCB1), both abundantly expressed in the kidney. In a long-term follow-up of a cohort of patients who had received kidney transplants between the years 1990 and 2005, we retrospectively investigated the effect of CYP3A4, CYP3A5, and ABCB1 polymorphisms in kidney graft donors on recipients' renal function and risk of subsequent graft loss. DNA samples from 227 donors and clinical data from the 259 respective recipients were analyzed. Graft loss was significantly associated with the presence of the ABCB1 variant haplotype 1236T/2677T/3435T in the donor (1236T/2677T/3435T vs. other haplotypes: hazard ratio = 9.346; 95% confidence interval (CI) (2.278-38.461); P = 0.0019) and with previous episodes of acute organ rejection (hazard ratio = 3.077; 95% CI (1.213-7.812); P = 0.0178). The variant haplotype was also associated with a greater decrease in renal function (homozygotes for TTT -3.047 mlxmin(-1)/year; heterozygotes for TTT -4.435 mlxmin(-1)/year; others -2.186 mlxmin(-1)/year; P = 0.0240). The study showed that the presence of ABCB1 polymorphisms in donors influences long-term graft outcome adversely with decrease in renal function and graft loss in transplant recipients receiving CsA. |
| اللغة: | English |
| تدمد: | 0009-9236 1532-6535 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d118ca95fc1d254bb653ffb1a4eab429Test https://europepmc.org/articles/PMC3017780Test/ |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....d118ca95fc1d254bb653ffb1a4eab429 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00099236 15326535 |
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