Association analysis of the NOD2 gene with susceptibility to graft-versus-host disease in a Japanese population

Int J Hematol. 2011 Jun;93(6):771-778. doi: 10.1007/s12185-011-0860-5. Epub 2011 May 15.


Members of the nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family participate in the innate immune system, exerting widespread effects on cytokine secretion, autophagy, and apoptosis. Recent studies in Caucasians revealed the association between mutants of NOD2, a member of the NLR family, and severity of acute graft-versus-host disease (GVHD). NOD2 polymorphism screening has been recommended for donor selection and risk assessment at bone marrow transplantation. To investigate whether NOD2 plays a role in the pathogenesis of GVHD in a Japanese population, we examined DNA from 142 bone marrow transplant patient/donor pairs to detect genetic variation in the NOD2 gene. No genetic variants of NOD2 were associated with the severity of acute GVHD in our patients. However, a weak association between a single nucleotide polymorphism in the NOD2 gene (R471C) and acute myeloid leukemia in the bone marrow patients (p = 0.029, odds ratio 4.08, 95% CI 1.22-13.67) was detected. This polymorphism was not prevalent in 479 Crohn's disease (CD) patients in Japan. These results suggest that, in the Japanese population, unlike the Caucasian, NOD2 is not a major contributor to susceptibility to severe acute GVHD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Crohn Disease / genetics
  • Crohn Disease / metabolism
  • Gene Expression Regulation
  • Genetic Predisposition to Disease / genetics*
  • Genotype
  • Graft vs Host Disease / genetics*
  • HEK293 Cells
  • Humans
  • Japan
  • Leukemia / genetics
  • Leukemia / metabolism
  • Nod2 Signaling Adaptor Protein / genetics*
  • Nod2 Signaling Adaptor Protein / metabolism
  • Polymorphism, Single Nucleotide / genetics


  • NOD2 protein, human
  • Nod2 Signaling Adaptor Protein