Polymorphisms in the heparanase gene in multiple myeloma association with bone morbidity and survival. (16th July 2014)

• Record Type: Journal Article
• Authors: Andersen, Niels F.; Vogel, Ulla; Klausen, Tobias W.; Gimsing, Peter; Gregersen, Henrik; Abildgaard, Niels; Vangsted, Annette J.
• Is Part Of: European journal of haematology. Volume 94:Number 1(2015:Jan.)
• Page Start: 60
• Page End: 66
• Publication Date: 2014-07-16
• Subjects: Hematology -- Periodicals; Blood -- Diseases -- Periodicals; Blood -- Periodicals; 616.15005
• DOI: 10.1111/ejh.12401
• Languages: English
• ISSNs: 0902-4441

Abstract

<abstract abstract-type="main" id="ejh12401-abs-0001"> <title>Abstract</title> <sec id="ejh12401-sec-0001" sec-type="section"> <title>Objectives</title> <p>In multiple myeloma, heparanase (<italic>HSPE</italic>) 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 <italic>HSPE</italic> gene with effect on gene function have been described, and some are associated with haematological malignancies.</p> </sec> <sec id="ejh12401-sec-0002" sec-type="section"> <title>Methods</title> <p>In this study, we evaluated four SNPs rs11099592, rs4364254, rs4693608 and rs6535455 in the <italic>HSPE</italic> 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).</p> </sec> <sec id="ejh12401-sec-0003" sec-type="section"> <title>Results</title> <p>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, <italic>P</italic> = 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, <italic>P</italic> = 0.002).</p> </sec> <sec id="ejh12401-sec-0004" sec-type="section"> <title>Conclusion</title> <p>The SNPs rs4693608 and rs6535455 in the <italic>HSPE</italic> 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 <italic>HSPE</italic> gene in multiple myeloma.</p> </sec> </abstract>