Angiogenesis related genes NOS3, CD14, MMP3 and IL4R are associated to VEGF gene expression and circulating levels in healthy adults

Saleh, A. and Stathopoulou, M. G. and Dadé, S. and Ndiaye, N. C. and Azimi-Nezhad, M. and Murray, H. and Masson, C. and Lamont, J. and Fitzgerald, P. and Visvikis-Siest, S. (2015) Angiogenesis related genes NOS3, CD14, MMP3 and IL4R are associated to VEGF gene expression and circulating levels in healthy adults. BMC Medical Genetics, 16 (1).

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Abstract

Background: 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. Methods: The 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. Results: The 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). Conclusions: Our 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. © Saleh et al.

Item Type: Article
Additional Information: Cited By :9 Export Date: 16 February 2020 CODEN: BMGMA Correspondence Address: Visvikis-Siest, S.; Université de Lorraine, UMR INSERM U 1122, IGE-PCV Interactions Gène-Environnement en Physiopathologie Cardio VasculaireFrance
Uncontrolled Keywords: CD14 IL4R MMP3 NOS3 VEGF CD14 antigen endothelial nitric oxide synthase high density lipoprotein cholesterol interleukin 4 receptor messenger RNA stromelysin triacylglycerol unclassified drug vasculotropin vasculotropin 121 vasculotropin 145 vasculotropin 165 vasculotropin 189 IL4 protein, human IL4R protein, human interleukin 4 interleukin 4 receptor alpha MMP3 protein, human NOS3 protein, human vasculotropin A VEGFA protein, human adult angiogenesis antiangiogenic activity Article CD14 gene DNA polymorphism environmental factor epistasis gene gene expression gene interaction gene structure genetic analysis human hypertension IL4R gene MMP3 gene normal human NOS3 gene obesity peripheral blood mononuclear cell protein binding protein function single nucleotide polymorphism smoking blood France gene expression profiling gene expression regulation gene frequency genetics longitudinal study metabolism Antigens, CD14 Humans Interleukin-4 Interleukin-4 Receptor alpha Subunit Longitudinal Studies Matrix Metalloproteinase 3 Neovascularization, Physiologic Nitric Oxide Synthase Type III Polymorphism, Single Nucleotide Vascular Endothelial Growth Factor A
Subjects: QU Biochemistry
Divisions: Mashhad University of Medical Sciences
Depositing User: mr lib5 lib5
Date Deposited: 08 Apr 2020 04:46
Last Modified: 08 Apr 2020 04:46
URI: http://eprints.mums.ac.ir/id/eprint/16605

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