Abstract
BackgroundVascular endothelial growth factor (VEGF) plays a key role in angiogenesis. The aim was to assess the genetic connections between the angiogenesis-related NOS3, CD14, MMP3, IL4R, IL4 genes and VEGF expression and plasma levels.MethodsThe associations between VEGF plasma levels with the polymorphisms of NOS3, CD14, MMP3, IL4R, and IL4 were assessed in 403 healthy unrelated adults. The epistatic and environmental interactions were explored, including four VEGF-related polymorphisms previously identified. The VEGF expression in peripheral blood mononuclear cells was quantified (n = 65) for the VEGF121, VEGF145, VEGF165, and VEGF189 isoforms.ResultsThe polymorphism rs1799983 of NOS3 was associated with the sum of all VEGF isoforms mRNA levels (P = 0.032) and VEGF145 (P = 0.033). Rs1800779 of NOS3 interacted with rs3918226 of the same gene and with the rs2569190 of CD14 (P = 0.022, P = 0.042, respectively) for VEGF plasma levels. Other epistatic interactions included the rs1801275 of IL4R with the rs6921438 (VEGF-related variant) and rs3025058 of MMP3 (P = 0.042, P = 0.010 respectively) and the rs2569190 of CD14 with the rs3025058 of MMP3 (P = 0.0119). We also identified an interaction of rs1800779 with obesity, high-density lipoprotein cholesterol and triglycerides (P = 0.018, P = 0.005, P = 0.043, respectively) as well as the interaction of rs6921438 with hypertension (P = 0.028).ConclusionsOur findings indicated that genetic variants of NOS3, CD14, MMP3 and IL4R are implicated in the determination of VEGF expression and plasma levels. Thus, they support the hypothesis that in physiological conditions there are complex biological relationships between pathways (such as angiogenesis and inflammation), which are involved in the development of chronic diseases.Electronic supplementary materialThe online version of this article (doi:10.1186/s12881-015-0234-6) contains supplementary material, which is available to authorized users.
Highlights
Vascular endothelial growth factor (VEGF) plays a key role in angiogenesis
In the present study, we have identified significant associations between genetic variants of Nitric Oxide Synthase (NOS3) with VEGF gene expression in a healthy population
Significant epistatic and gene × environment interactions have been identified for VEGF plasma levels involving polymorphisms of NOS3, Cluster of differentiation (CD14), Matrix metalloproteinase-3 (MMP3), Interleukin-4 receptor (IL4R) and VEGF-related single nucleotide polymorphisms (SNPs)
Summary
Vascular endothelial growth factor (VEGF) plays a key role in angiogenesis. The aim was to assess the genetic connections between the angiogenesis-related NOS3, CD14, MMP3, IL4R, IL4 genes and VEGF expression and plasma levels. Angiogenesis is the procedure of development of new vessels from the existing vasculature. One of the most potent angiogenesis regulators is the vascular endothelial growth factor A (VEGF-A or more commonly known as VEGF). VEGF is a highly conserved, disulfide-bonded dimeric glycoprotein of 34–46 kDa. VEGF is a highly conserved, disulfide-bonded dimeric glycoprotein of 34–46 kDa Other regulators of angiogenesis include the nitric oxide synthase (NOS3), the CD14+ monocytes, the matrix metalloproteinases (MMPs), and the interleukin 4 (IL4). NOS3 provides continuous local production of nitric oxide (NO). NO is an important angiogenesis mediator and/or effector involved in endothelial function and
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
