title: Donor TLR9 gene tagSNPs influence susceptibility to aGVHD and CMV reactivation in the allo-HSCT setting without polymorphisms in the TLR4 and NOD2 genes.
abstract: Owing to ethnicity of the population, those best confirmed polymorphisms in the TLR (toll-like receptor)4 and NOD2 genes with significantly prognostic impact on allogeneic hematopoietic SCT (allo-HSCT) seem to be more applicable to Europeans and are nonpolymorphic in the Asian population. The influence of innate immunity gene polymorphisms on the outcomes of allo-HSCT in those populations has been questioned. We evaluated the influence of 10 candidate single nucleotide polymorphisms (SNPs) in the TLR1, TLR2, TLR3, TLR8 and TLR9 genes on the outcomes of allo-HSCT in a Chinese population including 138 pairs of patients and unrelated donors and a second cohort of 102 pairs of patients and HLA-identical sibling donors. We found that two tagSNPs in the TLR9 gene in the donor side, +1174 A/G (rs352139) and +1635 C/T (rs352140), influenced the risk of acute GVHD (aGVHD) and CMV reactivation. Furthermore, the presence of the susceptible haplotype (A-C) in donor may be an informative predicator of worse OS at 5 years compared with those with the G-C and G-T haplotypes (58% vs 82.9%, P=0.024). Our data suggested an unrecognized association between donor TLR9 tagSNPs and the risk of HSCT-related complications in a population without polymorphisms in the TLR4 and NOD2 genes.
authors.affiliation: 1] Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China [2] Department of Haematology, Guangzhou Liuhuaqiao Hospital, Guangzhou, Guangdong, China.
authors.forename: H W
authors.initials: HW
authors.lastname: Xiao
authors.affiliation: Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
authors.forename: X Y
authors.initials: XY
authors.lastname: Lai
authors.affiliation: Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
authors.forename: J M
authors.initials: JM
authors.lastname: Shi
authors.affiliation: Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
authors.forename: Y M
authors.initials: YM
authors.lastname: Tan
authors.affiliation: Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
authors.forename: J S
authors.initials: JS
authors.lastname: He
authors.affiliation: Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
authors.forename: W Z
authors.initials: WZ
authors.lastname: Xie
authors.affiliation: Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
authors.forename: W Y
authors.initials: WY
authors.lastname: Zheng
authors.affiliation: Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
authors.forename: X J
authors.initials: XJ
authors.lastname: Ye
authors.affiliation: Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
authors.forename: X H
authors.initials: XH
authors.lastname: Yu
authors.affiliation: Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Cai
authors.affiliation: Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
authors.forename: M F
authors.initials: MF
authors.lastname: Lin
authors.affiliation: Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
authors.forename: H
authors.initials: H
authors.lastname: Huang
mesh_terms: D005260:Female; D005838:Genotype; D006086:Graft vs Host Disease / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D008297:Male; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D014019:Tissue Donors; D051197:Toll-Like Receptor 4 / Q000235:genetics* / Q000378:metabolism; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D053473:Nod2 Signaling Adaptor Protein; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4