Title:Toll-like Receptor 4 Gene Polymorphisms in Chinese Population After Allogeneic Hematopoietic Stem Cell Transplantation
Volume: 16
Issue: 2
Author(s): Yi Zhao, Yujie Zhang, Jie Zhou, Lijuan Wang, Jimin Shi, Yamin Tan, Yi Luo, He Huang and Zhen Cai*
Affiliation:
- Department of Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang,China
Keywords:
Toll-like receptor 4, polymorphisms, graft-versus-host disease, mutation, chinese population, pathogenesis.
Abstract:
Objectives: Graft-versus-host disease (GVHD) is the most common complication after
hematopoietic stem cell transplantation (HSCT) and remains to be a major cause of mortality.
Activation of toll-like receptor 4 (TLR-4) by lipopolysaccharide induces the NF-κB signaling
pathway to release critical proinflammatory cytokines and increases the recipient response to
GVHD. In order to clarify the role of TLR-4 in the occurrence of acute GVHD after HSCT, we
collected 208 samples from HSCT recipients and their human lecucyte antigen identical donors to
test the hypothesis that TLR-4polymorphism in the recipients or donors influence the risk of acute
GVHD in allogeneic HSCT recipients.
Methods: TLR-4 Asp299Gly and Thr399Ile polymorphisms of each sample were examined by
using DNA sequencing and polymerase chain reaction-restriction fragment length polymorphism
methods.
Results: No homozygous or heterozygous variant alleles of the Asp299Gly or Thr339Ile
polymorphism were detected in any samples in our study. Our results demonstrate that TLR-4
Asp299Gly and Thr399Ile polymorphisms might be very rare in the Chinese population (Eastern
China and Taiwan region).
Conclusion: The results of this study cannot confirm the role of TLR-4 mutations in the
pathogenesis of GVHD in humans, yet we reach a definite conclusion by a TLR-4 knockout
murine GVHD model in our ongoing project.
