title: Toll-like receptor 9, NOD2 and IL23R gene polymorphisms influenced outcome in AML patients transplanted from HLA-identical sibling donors.
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.
authors.affiliation: Department of Bone Marrow Transplantation, University Hospital of Essen, Essen, Germany. ahmet.elmaagacli@uni-duisburg-essen.de
authors.forename: A H
authors.initials: AH
authors.lastname: Elmaagacli
authors.forename: N
authors.initials: N
authors.lastname: Steckel
authors.forename: M
authors.initials: M
authors.lastname: Ditschkowski
authors.forename: Y
authors.initials: Y
authors.lastname: Hegerfeldt
authors.forename: H
authors.initials: H
authors.lastname: Ottinger
authors.forename: R
authors.initials: R
authors.lastname: Trenschel
authors.forename: M
authors.initials: M
authors.lastname: Koldehoff
authors.forename: D W
authors.initials: DW
authors.lastname: Beelen
mesh_terms: D006086:Graft vs Host Disease / Q000235:genetics; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000401:mortality; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000601:surgery*; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics*; D011110:Polymorphism, Genetic; D018123:Receptors, Interleukin / Q000235:genetics*; D035781:Siblings; D015996:Survival Rate; D014019:Tissue Donors; D051217:Toll-Like Receptor 9 / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: C515500:IL23R protein, human; D053473:Nod2 Signaling Adaptor Protein; D018123:Receptors, Interleukin; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9