Document Detail

Genetic variations in the heparanase gene (HPSE) associate with increased risk of GVHD following allogeneic stem cell transplantation: effect of discrepancy between recipients and donors.
MedLine Citation:
PMID:  20075159     Owner:  NLM     Status:  MEDLINE    
Graft-versus-host disease (GVHD) is the most common cause of nonrelapse mortality and morbidity after hematopoietic stem cell transplantation (HSCT). The well-documented involvement of heparanase in the process of inflammation and autoimmunity led us to investigate an association between HPSE gene single-nucleotide polymorphisms (SNPs) and the risk of GVHD. The present study indicates a highly significant correlation of HPSE gene SNPs rs4693608 and rs4364254 and their combination with the risk of developing acute GVHD. Moreover, the study revealed that discrepancy between recipient and donor in these SNPs may elevate significantly the risk of acute GVHD. This association was statistically significant when the recipients possessed genotype combinations dictating higher levels of heparanase compared with their human leukocyte antigen (HLA)-matched donors. In addition, HPSE gene SNPs disclosed a correlation with extensive chronic GVHD, nonrelapse mortality, and overall survival. Our study indicates involvement of heparanase in the development of acute and extensive chronic GVHD. Moreover, it suggests a possible mechanism for the aggressive behavior of T lymphocytes leading to GVHD when the recipients possess genotype combinations that dictate high levels of heparanase mRNA compared with their HLA-matched donors expressing low levels of heparanase.
Olga Ostrovsky; Avichai Shimoni; Avital Rand; Israel Vlodavsky; Arnon Nagler
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-01-14
Journal Detail:
Title:  Blood     Volume:  115     ISSN:  1528-0020     ISO Abbreviation:  Blood     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-03-19     Completed Date:  2010-04-13     Revised Date:  2014-09-12    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2319-28     Citation Subset:  AIM; IM    
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MeSH Terms
Acute Disease
Chronic Disease
Gene Frequency / genetics
Genetic Predisposition to Disease*
Glucuronidase / genetics*
Graft vs Host Disease / enzymology*,  genetics*,  prevention & control
Hematopoietic Stem Cell Transplantation* / mortality
Middle Aged
Multivariate Analysis
Polymorphism, Single Nucleotide / genetics*
Survival Analysis
Tissue Donors*
Transplantation Conditioning
Transplantation, Homologous
Young Adult
Grant Support
R01 CA106456/CA/NCI NIH HHS; R01-CA106456/CA/NCI NIH HHS
Reg. No./Substance:
EC 3.2.1.-/heparanase; EC

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