Impact of NOD2/CARD15 haplotypes on the outcome after kidney transplantation

Chronic allograft nephropathy and (cardiovascular) death with functioning graft are major causes of late graft loss. NOD2/CARD15 (nucleotide oligomerization domain-2/caspase-recruiting activating domain-15), an intracellular receptor, that is part of the innate immunity repertoire, has convincingly been shown to be involved in infection/inflammation-associated diseases. Specifically, NOD2/CARD15 polymorphisms are clearly associated with Crohn's disease and transplant-associated mortality after bone marrow transplantation. The aim of this study was to clarify the relevance of NOD2/CARD15-haplotypes in kidney transplantation. Three hundred fifty-two patients receiving their first kidney transplant were genotyped for the three major NOD2/CARD15 polymorphisms R702W, G908R and 1007fs with subsequent reconstruction of the different haplotypes. Four different NOD2/CARD15-haplotypes were observed in our population [CG(-): 89.8%, CGC: 3.5%, CC(-): 1.6%, TG(-): 5.1%). After stratifying the different haploypes into diplotypes (wild type: CG(-)/CG(-), n = 284, mutated haplotype, n = 68) we found a significant association with all-cause and cardiovascular mortality, also after adjusting to different covariates, and (only) in univariate analysis with graft survival. In conclusion, we found different effects of the NOD2/CARD15-haplotypes on disorders, like cardiovascular and all-cause mortality, which may be considered at least in part as chronic inflammation driven. Further studies are needed to confirm and work out the association between these disorders and the NOD2/CARD15-haplotypes.