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The NOTCH pathway is known to be important in the pathogenesis of calcific aortic valve disease, possibly through regulators of osteoprotegerin (OPG), receptor activator of nuclear factor <jats:italic>\u03ba<\/jats:italic>B (RANK), and its ligand (RANKL) system. The<jats:italic> purpose<\/jats:italic> of the present study was to search for possible associations between<jats:italic> NOTCH1<\/jats:italic> gene mutations and circulating levels of OPG and soluble RANKL (sRANKL) in patients with aortic stenosis (AS).<jats:italic> Methods<\/jats:italic>. The study was performed on 61 patients with AS including 31 with bicuspid and 30 with tricuspid aortic valves. We applied a strategy of targeted mutation screening for 10 out of 34 exons of the<jats:italic> NOTCH1<\/jats:italic> gene by direct sequencing. Serum OPG and sRANKL levels were assessed.<jats:italic> Results<\/jats:italic>. In total, 6 genetic variants of the<jats:italic> NOTCH1<\/jats:italic> gene including two new mutations were identified in the study group. In an age- and arterial hypertension-adjusted multivariable regression analysis, the serum OPG levels and the OPG\/sRANKL ratio were correlated with<jats:italic> NOTCH1<\/jats:italic> missense variants. All studied missense variants in NOTCH1 gene were found in Ca(2+)-binding EGF motif of the NOTCH extracellular domain bound to Delta-like 4.<jats:italic> Conclusion<\/jats:italic>. Our results suggest that the OPG\/RANKL\/RANK system might be directly influenced by genetic variants of NOTCH1 in aortic valve calcification.<\/jats:p>","DOI":"10.1155\/2017\/6917907","type":"journal-article","created":{"date-parts":[[2017,1,26]],"date-time":"2017-01-26T21:53:19Z","timestamp":1485467599000},"page":"1-10","source":"Crossref","is-referenced-by-count":26,"title":["NOTCH1 Mutations in Aortic Stenosis: Association with Osteoprotegerin\/RANK\/RANKL"],"prefix":"10.1155","volume":"2017","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8656-3191","authenticated-orcid":true,"given":"Olga","family":"Irtyuga","sequence":"first","affiliation":[{"name":"Federal Almazov Medical Research Centre, St. Petersburg, Russia"},{"name":"Institute of translational Medicine, ITMO University, St. Petersburg, 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