Toll-like receptor 9, NOD2 and IL23R gene polymorphisms influenced outcome in AML patients transplanted from HLA-identical sibling donors

Bone Marrow Transplant. 2011 May;46(5):702-8. doi: 10.1038/bmt.2010.166. Epub 2010 Jul 12.

Abstract

We evaluated the influence of gene polymorphisms of TLR9 (T1237C; T1486C), IL23R (A1142G), and NOD2 SNP8 (R702W), SNP12 (G908R) and SNP13 (1007fs) on outcome of hematopoietic SCT in a homogenous group of 142 AML patients after non-T-cell-depleted myeloablative transplantation from HLA-identical sibling donors. In our retrospective study, we found that TLR9 gene variant at 1486 influenced transplant outcome. Estimated 5-year OS in patients with the CC gene variant of TLR9 was 70.2% compared with 44.8% (P<0.027) in patients with TC/TT of TLR9 gene. No significant influences on 5-year OS were found for gene polymorphisms of NOD2 or IL23R (A1142G) in this study group. The 5-year treatment-related mortality was lowest in patients with CC gene variant of TLR9 (7.8 vs 23.1%; NS). Acute GVHD grade III-IV was higher in patients with NOD2 gene variants (28 vs 12.8%; P=0.065). In contrast, patients transplanted from donors with the gene variant of IL23R had no occurrence of severe acute GVHD grade III-IV (0 vs 18.4%; P<0.048). However, multivariate analysis confirmed the influence of NOD2 gene variants on the occurrence of acute GVHD grade II-IV after transplant. These results suggest that the gene variants of TLR9, NOD2 and Il23R had influence on the outcome of transplant.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Graft vs Host Disease / genetics
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Hematopoietic Stem Cell Transplantation / mortality
  • Humans
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / surgery*
  • Nod2 Signaling Adaptor Protein / genetics*
  • Polymorphism, Genetic
  • Receptors, Interleukin / genetics*
  • Siblings
  • Survival Rate
  • Tissue Donors
  • Toll-Like Receptor 9 / genetics*
  • Treatment Outcome

Substances

  • IL23R protein, human
  • Nod2 Signaling Adaptor Protein
  • Receptors, Interleukin
  • TLR9 protein, human
  • Toll-Like Receptor 9