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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.    Electronic supplementary material  The online version of this article (doi:10.1186/s12881-015-0234-6) contains supplementary material, which is available to authorized users.

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