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  • Title: Impact of NOD2/CARD15 haplotypes on the outcome after kidney transplantation.
    Author: Krüger B, Böger CA, Schröppel B, Obed A, Hoffmann U, Murphy BT, Fischereder M, Holler E, Banas B, Krämer BK.
    Journal: Transpl Int; 2007 Jul; 20(7):600-7. PubMed ID: 17498224.
    Abstract:
    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 haplotypes 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.
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