ISSN: 0970-938X (Print) | 0976-1683 (Electronic)
An International Journal of Medical Sciences
Sofia Siest
University of Lorraine, France
Posters & Accepted Abstracts : Biomed Res
DOI: 10.4066/biomedicalresearch-C8-023
Vascular endothelial growth factor�¢����A (VEGF�¢����A) is implicated in angiogenesis, lymphangiogenesis, vascular permeability and haematopoiesis. It is associated with numerous pathologies including cardio-vascular diseases and several types of cancer. We specifically developed an integrative systems biology strategy for clinical improvement of this biomarker. A high heritability of this trait, 60% was estimated in the STANISLAS cohort giving us the needed arguments to continue for a deep characterization of the genetic component of VEGF�¢����A levels. Therefore, we searched, by a Genome Wide Association Study (GWAS), the VEGF�¢����A genetic variants and the inter-connexions of these biomarkers with other diseaseassociated molecules in healthy populations. Functional transcriptomic analyses were performed in peripheral blood mononuclear cells (PBMCs). Four polymorphisms (rs6921438, rs4416670, rs6993770, rs10738760) explaining ~50% of VEGF�¢����A heritability were identified. These variants, directly or via gene x environment interactions had significant effects on HDL, LDL, TNF-a, IL-6, E selectin and ICAM-1 plasma levels. SNP rs6993770 was shown to increase VEGF121 mRNA levels and rs4416670 was associated with L-selectin expression. Recently, thanks to a meta-GWAS, we identified 6 additional rs further explaining VEGF�¢����A levels variability and ongoing investigations focus on clinical implementation of the �¢�����¢����omics�¢���� determinants of this biomarker. Our integrative strategy illustrates an improved exemple to be applied for every biomarker with high heritability levels, consequently with potential interest in personalised medicine
E-mail:
sophie.visvikis-siest@inserm.fr
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