title: Polymorphisms in the heparanase gene in multiple myeloma association with bone morbidity and survival.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors: Department of Haematology, Aarhus University Hospital, Aarhus, Denmark.
authors: Niels F
authors: NF
authors: Andersen
authors: Ulla
authors: U
authors: Vogel
authors: Tobias W
authors: TW
authors: Klausen
authors: Peter
authors: P
authors: Gimsing
authors: Henrik
authors: H
authors: Gregersen
authors: Niels
authors: N
authors: Abildgaard
authors: Annette J
authors: AJ
authors: Vangsted
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001847:Bone Diseases / Q000209:etiology* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency; D005838:Genotype; D005966:Glucuronidase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000150:complications* / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D010014:Osteolysis / Q000235:genetics; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D017211:Treatment Failure; D016896:Treatment Outcome; D000099175:Heparanase
chemical_list: D005966:Glucuronidase; D000099175:Heparanase
keywords: bone disease; heparanase (HSPE); multiple myeloma; single nucleotide polymorphisms (SNPs); survival