Article open access publication

Polymorphisms in the heparanase gene in multiple myeloma association with bone morbidity and survival

European Journal Of Haematology, Wiley, ISSN 1600-0609

Volume 94, 1, 2015

DOI:10.1111/ejh.12401, Dimensions: pub.1015332452, PMID: 24954766,



  1. (1) Aarhus University Hospital, grid.154185.c, Central Denmark Region
  2. (2) National Research Centre for the Working Environment, grid.418079.3
  3. (3) Department of Haematology, University Hospital of Copenhagen at Herlev, Herlev, Denmark
  4. (4) Department of Haematology, University Hospital of Copenhagen at Rigshospitalet, Copenhagen, Denmark
  5. (5) Aalborg Hospital, grid.27530.33, North Denmark Region
  6. (6) Odense University Hospital, grid.7143.1, Southern Denmark Region






OBJECTIVES: In multiple myeloma, heparanase (HSPE) is involved in myeloma cell growth, angiogenesis, osteoclastogenesis and shedding of syndecan-1, a key player in myeloma pathophysiology. Different single nucleotide polymorphisms (SNPs) in the HSPE gene with effect on gene function have been described, and some are associated with haematological malignancies. METHODS: In this study, we evaluated four SNPs rs11099592, rs4364254, rs4693608 and rs6535455 in the HSPE gene in 348 newly diagnosed multiple myeloma patients with focus on bone morbidity (lytic bone disease and vertebral fractures) and outcome after high-dose chemotherapy with stem cell support (HDT). RESULTS: We observed that homozygous carriers of the rs4693608 wild-type A-allele had a higher frequency of vertebral fractures compared to carriers of the variant G-allele, P = 0.02. In multivariate analysis, homozygous carriers of the rs6535455 variant T-allele had a longer survival than homo- and heterozygous carriers of the wild-type C-allele, hazard ratio 0.3 (95% CI 0.1-0.7, P = 0.002). CONCLUSION: The SNPs rs4693608 and rs6535455 in the HSPE gene may influence bone morbidity and outcome in multiple myeloma. Our results are an interesting observation but can be chance findings and need confirmation in studies exploring the functional role of SNPs in the HSPE gene in multiple myeloma.


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