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Lieb, Wolfgang; Chen, Ming-Huei; Larson, Martin G.; Safa, Radwan; Teumer, Alexander; Baumeister, Sebastian E.; Lin, Honghuang; Smith, Holly M.; Koch, Manja; Lorbeer, Roberto; Völker, Uwe; Nauck, Matthias; Völzke, Henry; Wallaschofski, Henri; Sawyer, Douglas B.; Vasan, Ramachandran S.

Genome-Wide Association Study for Endothelial Growth Factors

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  • Medientyp: E-Artikel
  • Titel: Genome-Wide Association Study for Endothelial Growth Factors
  • Beteiligte: Lieb, Wolfgang; Chen, Ming-Huei; Larson, Martin G.; Safa, Radwan; Teumer, Alexander; Baumeister, Sebastian E.; Lin, Honghuang; Smith, Holly M.; Koch, Manja; Lorbeer, Roberto; Völker, Uwe; Nauck, Matthias; Völzke, Henry; Wallaschofski, Henri; Sawyer, Douglas B.; Vasan, Ramachandran S.
  • Erschienen: Ovid Technologies (Wolters Kluwer Health), 2015
  • Erschienen in: Circulation: Cardiovascular Genetics, 8 (2015) 2, Seite 389-397
  • Sprache: Englisch
  • DOI: 10.1161/circgenetics.114.000597
  • ISSN: 1942-3268; 1942-325X
  • Schlagwörter: Genetics (clinical) ; Cardiology and Cardiovascular Medicine ; Genetics
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:sec> <jats:title>Background—</jats:title> <jats:p>Endothelial growth factors including angiopoietin-2 (Ang-2), its soluble receptor Tie-2 (sTie-2), and hepatocyte growth factor play important roles in angiogenesis, vascular remodeling, local tumor growth, and metastatic potential of various cancers. Circulating levels of these biomarkers have a heritable component (between 13% and 56%), but the underlying genetic variation influencing these biomarker levels is largely unknown.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods and Results—</jats:title> <jats:p> We performed a genome-wide association study for circulating Ang-2, sTie-2, and hepatocyte growth factor in 3571 Framingham Heart Study participants and assessed replication of the top hits for Ang-2 and sTie-2 in 3184 participants of the Study of Health in Pomerania. In multivariable-adjusted models, sTie-2 and hepatocyte growth factor concentrations were associated with single-nucleotide polymorphisms in the genes encoding the respective biomarkers (top <jats:italic>P</jats:italic> =2.40×10 <jats:sup>−65</jats:sup> [rs2273720] and 3.64×10 <jats:sup>−19</jats:sup> [rs5745687], respectively). Likewise, rs2442517 in the <jats:italic>MCPH1</jats:italic> gene (in which the <jats:italic>Ang-2</jats:italic> gene is embedded) was associated with Ang-2 levels ( <jats:italic>P</jats:italic> =5.05×10 <jats:sup>−8</jats:sup> in Framingham Heart Study and 8.39×10 <jats:sup>−5</jats:sup> in Study of Health in Pomerania). Furthermore, single-nucleotide polymorphisms in the <jats:italic>AB0</jats:italic> gene were associated with sTie-2 (top single-nucleotide polymorphism rs8176693 with <jats:italic>P</jats:italic> =1.84×10 <jats:sup>−33</jats:sup> in Framingham Heart Study; <jats:italic>P</jats:italic> =2.53×10 <jats:sup>−30</jats:sup> in Study of Health in Pomerania) and Ang-2 (rs8176746 with <jats:italic>P</jats:italic> =2.07×10 <jats:sup>−8</jats:sup> in Framingham Heart Study; <jats:italic>P</jats:italic> =0.001 in Study of Health in Pomerania) levels on a genome-wide significant level. The top genetic loci were explained between 1.7% (Ang-2) and 11.2% (sTie-2) of the interindividual variation in biomarker levels. </jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions—</jats:title> <jats:p>Genetic variation contributes to the interindividual variation in growth factor levels and explains a modest proportion of circulating hepatocyte growth factor, Ang-2, and Tie-2. This may potentially contribute to the familial susceptibility to cancer, a premise that warrants further studies.</jats:p> </jats:sec>
  • Zugangsstatus: Freier Zugang