A comprehensive genotype-phenotype interaction of different Toll-like receptor variations in a renal transplant cohort.
Résumé
Background: To date, the impact of the Toll-like receptor (TLR) system on early and late kidney transplantation outcome such as acute rejection episodes or cardiovascular morbidity and mortality has still not been conclusively elucidated. Genetically determined alterations in TLR expression exhibit a possibility to evaluate their role in transplantation. In this study we sought to determine a comprehensive genotype-phenotype association with early and late allograft outcomes. Methods: We studied 11 SNPs in TLR2, TLR3, TLR4, TLR5, TLR9 and within a co-molecule CD14 in 265 patients receiving their first kidney transplant and associated them with the occurrence of delayed graft function, acute rejection episodes or cardiovascular mortality or morbidity. Results: Acute rejection episodes were significantly more frequent in patients carrying the TLR3 TT/CT-allele (43.8% vs. 25.8%, p=0.001) as were rates of DGF (21.4% vs. 12.0%, p=0.030). Furthermore, TLR9 was significantly involved in the occurrence of MACE (TLR9 -1237, p=0.03). Interestingly there was no significant effect of any TLR-polymorphism on graft survival or renal function and the incidence of any infection, including CMV-infection. Conclusion: In our study in renal transplant recipients suggests the TLR system to be involved in both acute rejection and MACE. Modulation of the TLR system may be promising targets in future therapeutic strategies.
Origine : Fichiers produits par l'(les) auteur(s)
Loading...