title: Impact of NOD2/CARD15 haplotypes on the outcome after kidney transplantation.
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.
authors.affiliation: Klinik und Poliklinik für Innere Medizin II-Nephrologie, Universität Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany. bernd.krueger@klinik.uni-regensburg.de
authors.forename: Bernd
authors.initials: B
authors.lastname: Krüger
authors.forename: Carsten A
authors.initials: CA
authors.lastname: Böger
authors.forename: Bernd
authors.initials: B
authors.lastname: Schröppel
authors.forename: Aiman
authors.initials: A
authors.lastname: Obed
authors.forename: Ute
authors.initials: U
authors.lastname: Hoffmann
authors.forename: Barbara T
authors.initials: BT
authors.lastname: Murphy
authors.forename: Michael
authors.initials: M
authors.lastname: Fischereder
authors.forename: Ernst
authors.initials: E
authors.lastname: Holler
authors.forename: Bernhard
authors.initials: B
authors.lastname: Banas
authors.forename: Bernhard K
authors.initials: BK
authors.lastname: Krämer
mesh_terms: D000328:Adult; D000368:Aged; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D051799:Delayed Graft Function / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D006084:Graft Rejection / Q000453:epidemiology / Q000235:genetics; D006085:Graft Survival / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D015994:Incidence; D007674:Kidney Diseases / Q000235:genetics* / Q000601:surgery*; D016030:Kidney Transplantation / Q000401:mortality; D008297:Male; D008875:Middle Aged; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics*; D011110:Polymorphism, Genetic; D011183:Postoperative Complications; D016896:Treatment Outcome
chemical_list: C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein