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

BMC Medical Genetics

Sophie Visvikis-Siest⁴  Peter Fitzgerald¹  John Lamont¹  Christine Masson²  Helena Murray¹  Mohsen Azimi-Nezhad³  Ndeye Coumba Ndiaye²  Sébastien Dadé²  Maria G. Stathopoulou²  Abdelsalam Saleh² 

[1] Randox Laboratories, Crumlin, UK;UMR INSERM U 1122, IGE-PCV “Interactions Gène-Environnement en Physiopathologie Cardio Vasculaire”, Université de Lorraine, Nancy F-54000, France;Department of Medical Genetics, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran;Geriatric Service, University Hospital of Nancy, Nancy, France

关键词: IL4R;    MMP3;    CD14;    NOS3;    VEGF;   

Others  :  1230728
DOI  :  10.1186/s12881-015-0234-6

 received in 2014-10-21, accepted in 2015-09-23,  发布年份 2015

【 摘 要 】

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.

【 授权许可】

   
2015 Saleh et al.

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