Polymorphisms within epithelial receptors: NOD2/CARD15.
Genetic risk assessment in the setting of allogeneic stem cell transplantation is one of the major goals to optimise future prophylaxis and treatment of patients: our group has focused on analysis of single-nucleotide polymorphisms (SNPs) within the intracytoplasmatic receptor NOD2/CARD15, which recognizes the bacterial cell wall compound muramyl-dipeptide and induces nuclear factor-kappaB-mediated inflammation. By performing TaqMan PCR of the three major SNPs also identified as risk factors in Crohn's disease in donors and recipients, we were able to demonstrate a major association of NOD2/CARD15 SNPs with the occurrence of severe graft-vs-host disease and resulting treatment-related mortality following human leukocyte antigen-identical sibling transplantation. Although these data need confirmation in further prospective trials, this association may not only be used for risk assessment but also point to a major pathophysiological interaction of dysregulated activation of the innate immune system and specific alloreaction.
Brenmoehl
Julia
J
Department of Internal Medicine I, University Medical Centre of Regensburg, Regensburg, Germany.
Holler
Ernst
E
Rogler
Gerhard
G
D000483:Alleles; D004247:DNA / Q000302:isolation & purification; D004252:DNA Mutational Analysis / Q000379:methods*; D004847:Epithelial Cells / Q000378:metabolism*; D006086:Graft vs Host Disease / Q000235:genetics* / Q000401:mortality; D006801:Humans; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D018570:Risk Assessment / Q000379:methods; D013223:Statistics as Topic / Q000379:methods; D016019:Survival Analysis
C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D004247:DNA