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Bone Marrow Transplantation (2011) 46, 400407
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ORIGINAL ARTICLE
Relationship between TNFA, TNFB and TNFRII gene polymorphisms and outcome after unrelated hematopoietic cell transplantationin a Chinese population
HW Xiao1,2,3, XY Lai1,3, Y Luo1, JM Shi1, YM Tan1, JS He1, WZ Xie1, L Li1, XL Zhu1, JJ Zhu1, J Sun1,
GQ Wei1, L Jin1, LZ Liu1, KN Wu1, XH Yu1, Z Cai1, MF Lin1, XJ Ye1 and H Huang1
1Bone Marrow Transplantation Center, The First Afliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China and 2Department of Haematology, Guangzhou Liuhuaqiao Hospital, Guangzhou, Guangdong Province, China
This study aimed to analyze the association between cytokine gene polymorphisms and outcome following allogeneic hematopoietic SCT (allo-HSCT). A total of 138 unrelated donor/recipient pairs who underwent allo-HSCT from 2001 to 2009 were tested for TNFA-1031 (T4C), -863 (C4A), -857 (C4T), -238 (G4A), TNFB 252 (A4G)
and TNFRII codon 196 (T4G) single nucleotide polymorphisms by multiplex SnaPshot analysis. Transplantation involving recipients and/or donors with TNFA-857 C/C genotype or TNFB 252 G allele-positivity resulted in a
higher incidence of acute GVHD (aGVHD), which was independent of HLA mismatching. In multivariate analysis, TNFA-857 C/C genotype donors (relative risk (RR) 2.29,
P 0.006) and TNFB 252 G allele-positive recipients
(RR 1.789, P 0.036) were found to be signicantly
associated with an increased incidence of aGVHD. TNFA-857 C/C genotype donors (RR 3.748, P 0.002) and
TNFB 252 G allele-positive recipients (RR 1.823,
P 0.063) were also associated with the development of
grades IIIV aGVHD. TNFRII polymorphism in recipients was also related to relapse rate, but no signicant associations were found between TNFA, TNFB or TNFRII 196 genotype and cGVHD, relapse or overall survival after transplantation. These results provide the rst report of an association between TNFA, TNFB and TNFRII polymorphic features and outcome of allo-HSCT in a Chinese population, and suggest an interaction between TNFA-857 and TNFB 252 genotypes and risk of aGVHD.
Bone Marrow Transplantation (2011) 46, 400407; doi:http://dx.doi.org/10.1038/bmt.2010.135
Web End =10.1038/bmt.2010.135 ; published online 14 June 2010 Keywords: hematopoietic SCT; TNFA; TNFB; TNFRII; polymorphism; GVHD
IntroductionDespite advances in HLA-typing methods and post transplantation immune suppression, GVHD remains a signicant cause of transplant-related mortality and morbidity following allogeneic hematopoietic SCT...