To date, the impact of the TLR (Toll-like receptor) system on early and late kidney transplantation outcome, such as ARE (acute rejection episodes) or cardiovascular morbidity and mortality, has still not been elucidated conclusively. Genetically determined alterations in TLR expression exhibit a possibility to evaluate their role in transplantation. In the present study, we sought to determine a comprehensive genotype–phenotype association with early and late allograft outcomes. We studied 11 SNPs (single nucleotide polymorphisms) in TLR2, TLR3, TLR4, TLR5, TLR9 and within a co-molecule CD14 in 265 patients receiving their first kidney transplant and the association of these with the occurrence of DGF (delayed graft function), ARE or MACE (major adverse cardiovascular events). ARE were significantly more frequent in patients carrying the TLR3 TT/CT allele (43.8 compared with 25.8%; P=0.001) as were rates of DGF (21.4 compared with 12.0%; P=0.030). Furthermore, TLR9 was significantly involved in the occurrence of MACE (TLR9 −1237; P=0.030). Interestingly, there was no significant effect of any TLR polymorphism on graft survival or renal function and the incidence of any infection, including CMV (cytomegalovirus) infection. In conclusion, our present study in renal transplant recipients suggests that the TLR system may be involved in both acute rejection and MACE. Modulation of the TLR system may be a promising target in future therapeutic strategies.
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Research Article|
September 06 2010
A comprehensive genotype–phenotype interaction of different Toll-like receptor variations in a renal transplant cohort
Bernd Krüger;
*V. Medizinische Klinik, Universitätsklinikum Mannheim, Medizinische Fakultät Mannheim der Universität Heidelberg, 68167 Mannheim, Germany
†Klinik und Poliklinik für Innere Medizin II, Universitätsklinikum Regensburg, 93053 Regensburg, Germany
Correspondence: Dr Bernd Krüger (email bernd.krueger@ruhr-uni-bochum.de).
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Miriam C. Banas;
Miriam C. Banas
†Klinik und Poliklinik für Innere Medizin II, Universitätsklinikum Regensburg, 93053 Regensburg, Germany
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Andreas Walberer;
Andreas Walberer
†Klinik und Poliklinik für Innere Medizin II, Universitätsklinikum Regensburg, 93053 Regensburg, Germany
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Carsten A. Böger;
Carsten A. Böger
†Klinik und Poliklinik für Innere Medizin II, Universitätsklinikum Regensburg, 93053 Regensburg, Germany
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Stefan Farkas;
Stefan Farkas
‡Klinik und Poliklinik für Chirurgie, Universitätsklinikum Regensburg, 93053 Regensburg, Germany
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Ute Hoffmann;
Ute Hoffmann
†Klinik und Poliklinik für Innere Medizin II, Universitätsklinikum Regensburg, 93053 Regensburg, Germany
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Michael Fischereder;
Michael Fischereder
§Medizinische Poliklinik Innenstadt, Klinikum der Ludwig-Maximillians-Universität München, 80336 München, Germany
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Bernhard Banas;
Bernhard Banas
†Klinik und Poliklinik für Innere Medizin II, Universitätsklinikum Regensburg, 93053 Regensburg, Germany
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Bernhard K. Krämer
Bernhard K. Krämer
*V. Medizinische Klinik, Universitätsklinikum Mannheim, Medizinische Fakultät Mannheim der Universität Heidelberg, 68167 Mannheim, Germany
†Klinik und Poliklinik für Innere Medizin II, Universitätsklinikum Regensburg, 93053 Regensburg, Germany
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Publisher: Portland Press Ltd
Received:
April 01 2010
Revision Received:
June 15 2010
Accepted:
July 06 2010
Accepted Manuscript online:
July 06 2010
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2010 Biochemical Society
2010
Clin Sci (Lond) (2010) 119 (12): 535–544.
Article history
Received:
April 01 2010
Revision Received:
June 15 2010
Accepted:
July 06 2010
Accepted Manuscript online:
July 06 2010
Citation
Bernd Krüger, Miriam C. Banas, Andreas Walberer, Carsten A. Böger, Stefan Farkas, Ute Hoffmann, Michael Fischereder, Bernhard Banas, Bernhard K. Krämer; A comprehensive genotype–phenotype interaction of different Toll-like receptor variations in a renal transplant cohort. Clin Sci (Lond) 1 December 2010; 119 (12): 535–544. doi: https://doi.org/10.1042/CS20100190
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