{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T22:29:11Z","timestamp":1761863351364},"reference-count":34,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2014,7,16]],"date-time":"2014-07-16T00:00:00Z","timestamp":1405468800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Dansk Kr\u00ef\u00bf\u00bdftforsknings Fond"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["European J of Haematology"],"published-print":{"date-parts":[[2015,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>In multiple myeloma, heparanase (<jats:italic><jats:styled-content style=\"fixed-case\">HSPE<\/jats:styled-content><\/jats:italic>) is involved in myeloma cell growth, angiogenesis, osteoclastogenesis and shedding of syndecan\u20101, a key player in myeloma pathophysiology. Different single nucleotide polymorphisms (<jats:styled-content style=\"fixed-case\">SNP<\/jats:styled-content>s) in the <jats:italic><jats:styled-content style=\"fixed-case\">HSPE<\/jats:styled-content><\/jats:italic> gene with effect on gene function have been described, and some are associated with haematological malignancies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, we evaluated four <jats:styled-content style=\"fixed-case\">SNP<\/jats:styled-content>s rs11099592, rs4364254, rs4693608 and rs6535455 in the <jats:italic><jats:styled-content style=\"fixed-case\">HSPE<\/jats:styled-content><\/jats:italic> gene in 348 newly diagnosed multiple myeloma patients with focus on bone morbidity (lytic bone disease and vertebral fractures) and outcome after high\u2010dose chemotherapy with stem cell support (<jats:styled-content style=\"fixed-case\">HDT<\/jats:styled-content>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We observed that homozygous carriers of the rs4693608 wild\u2010type A\u2010allele had a higher frequency of vertebral fractures compared to carriers of the variant G\u2010allele, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.02. In multivariate analysis, homozygous carriers of the rs6535455 variant T\u2010allele had a longer survival than homo\u2010 and heterozygous carriers of the wild\u2010type C\u2010allele, hazard ratio 0.3 (95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content> 0.1\u20130.7, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.002).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The <jats:styled-content style=\"fixed-case\">SNP<\/jats:styled-content>s rs4693608 and rs6535455 in the <jats:italic><jats:styled-content style=\"fixed-case\">HSPE<\/jats:styled-content><\/jats: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 <jats:styled-content style=\"fixed-case\">SNP<\/jats:styled-content>s in the <jats:italic><jats:styled-content style=\"fixed-case\">HSPE<\/jats:styled-content><\/jats:italic> gene in multiple myeloma.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ejh.12401","type":"journal-article","created":{"date-parts":[[2014,6,21]],"date-time":"2014-06-21T07:30:11Z","timestamp":1403335811000},"page":"60-66","source":"Crossref","is-referenced-by-count":8,"title":["Polymorphisms in the heparanase gene in multiple myeloma association with bone morbidity and survival"],"prefix":"10.1111","volume":"94","author":[{"given":"Niels F.","family":"Andersen","sequence":"first","affiliation":[{"name":"Department of Haematology Aarhus University Hospital Aarhus Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulla","family":"Vogel","sequence":"additional","affiliation":[{"name":"National Research Centre for Working Environment Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tobias W.","family":"Klausen","sequence":"additional","affiliation":[{"name":"Department of Haematology University Hospital of Copenhagen at Herlev Herlev Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Gimsing","sequence":"additional","affiliation":[{"name":"Department of Haematology University Hospital of Copenhagen at Rigshospitalet Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henrik","family":"Gregersen","sequence":"additional","affiliation":[{"name":"Department of Haematology Aalborg University Hospital Aalborg Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Niels","family":"Abildgaard","sequence":"additional","affiliation":[{"name":"Department of Haematology Odense University Hospital Odense Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annette J.","family":"Vangsted","sequence":"additional","affiliation":[{"name":"Department of Haematology University Hospital of Copenhagen at Rigshospitalet Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,7,16]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1119(00)00251-1"},{"key":"e_1_2_8_3_1","first-page":"112","article-title":"Expression of heparanase by platelets and circulating cells of the immune system: possible involvement in diapedesis and extravasation","volume":"12","author":"Vlodavsky I","year":"1992","journal-title":"Invasion Metastasis"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2404821"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.2007.00461.x"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1006\/scbi.2001.0420"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2006.06.004"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200113738"},{"key":"e_1_2_8_9_1","first-page":"8749","article-title":"High heparanase activity in multiple myeloma is associated with elevated microvessel density","volume":"63","author":"Kelly T","year":"2003","journal-title":"Cancer Res"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.16"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-08-043232"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V81.3.767.767"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.10.5077"},{"key":"e_1_2_8_14_1","doi-asserted-by":"crossref","first-page":"20013","DOI":"10.1016\/S0021-9258(17)32120-8","article-title":"Expression of syndecan\u20101 inhibits cell invasion into type I collagen","volume":"269","author":"Liebersbach BF","year":"1994","journal-title":"J Biol Chem"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0074-7696(01)07004-8"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-07-234757"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2004.05299.x"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V95.2.388"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.22411"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2006.06042.x"},{"key":"e_1_2_8_21_1","first-page":"7","article-title":"Impact on survival of high\u2010dose therapy with autologous stem cell support in patients younger than 60\u00a0yr with newly diagnosed multiple myeloma: a population\u2010based study. 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