A comprehensive genotype-phenotype interaction of different Toll-like receptor variations in a renal transplant cohort

Abstract

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. © The Authors Journal compilation © 2010 Biochemical Society.