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Graft-versus-host Disease

Donor TLR9 gene tagSNPs influence susceptibility to aGVHD and CMV reactivation in the allo-HSCT setting without polymorphisms in the TLR4 and NOD2 genes

Bone Marrow Transplantation volume 49, pages 241–247 (2014)Cite this article

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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.

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Acknowledgements

We would like to thank the Shanghai Genesky Bio-Tech Genetic Core Lab for their excellent technical assistance with sequencing analysis. We also thank the HLA Typing Laboratory of the Blood Center of the Zhejiang Province for their assistance. This work was supported in part by the Key Project of National Natural Science Foundation of China (81230014), National High Technology Research and Development Program of China (2012AA020905), National Natural Science Foundation of China (81100387, 81170501), foundation of the Zhejiang Educational Committee (Y201019151) and foundation of the Zhejiang Science Technology Department (N20080398).

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  1. Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China

    H W Xiao, Y Luo, X Y Lai, J M Shi, Y M Tan, J S He, W Z Xie, W Y Zheng, X J Ye, X H Yu, Z Cai, M F Lin & H Huang

  2. Department of Haematology, Guangzhou Liuhuaqiao Hospital, Guangzhou, Guangdong, China

    H W Xiao

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Xiao, H., Luo, Y., Lai, X. et al. Donor TLR9 gene tagSNPs influence susceptibility to aGVHD and CMV reactivation in the allo-HSCT setting without polymorphisms in the TLR4 and NOD2 genes. Bone Marrow Transplant 49, 241–247 (2014). https://doi.org/10.1038/bmt.2013.160

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