Interaction between Vascular Endothelial Growth Factor-A (rs2010963) Gene Polymorphisms and Dietary Diversity Score on Cardiovascular Risk Factors in Patients with Metabolic Syndrome

Abstract

Background: The vascular endothelial growth factor-A (VEGFA) family of cytokines regulates proliferation, angiogenesis, and migration of endothelial cells, increases vascular permeability, and controls thrombogenicity. Recent studies have suggested that the VEGFA gene plays an important role in the pathogenesis of metabolic syndrome and its related disorders. Dietary diversity score (DDS) has also been shown to have potential favorable effects against features of metabolic syndrome. This study examined the interactions between +405 VEGFA C/G (rs2010963) polymorphism and DDS on the metabolic and biochemical profile of metabolic syndrome. Therefore, in the current study, we aimed to evaluate the interaction between DDS and VEGFA rs2010963 gene polymorphisms in modification of metabolic risk factors including serum lipids, blood pressure, serum adiponectin, and matrix metalloproteinase (MMP)-3 concentrations in patients with metabolic syndrome.

Methods and materials: In the current cross-sectional study, 254 patients with metabolic syndrome were recruited. Measurements of blood pressure, anthropometric parameters, and dietary intakes were performed and the DDS was calculated. Biochemical variables including serum adiponectin concentrations, lipid profile, serum glucose, and MMP-3 concentrations were measured by enzyme-linked immunosorbent assay method (ELISA) and enzymatic colorimetric methods. Determination of +405 C/G VEGFA gene polymorphisms was performed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique.

Results: Patients in the lowest DDS quartile had higher insulin and homeostatic model assessment of insulin resistance (HOMA-IR), while patients in the highest DDS quartile had higher quantitative insulin check index (QUICKI; p < 0.05). Higher serum triglyceride and systolic blood pressure (SBP) values and lower serum adiponectin concentrations were also observed in lower DDS quartiles (p < 0.05). Patients with the CC genotype in the VEGFA rs2010963 polymorphism had significantly higher body mass index (BMI), fasting blood glucose, aspartate aminotransferase (AST), and alanine aminotransferase (ALT; p < 0.05) compared to patients with the other 2 genotypes. In lower quartiles of DDS, 30% of patients with metabolic syndrome had the GG genotype, while 30.4 and 30.8% of patients with metabolic syndrome in higher DDS quartiles had GC and CC genotypes, respectively (p = 0.04).

Conclusion: Our study found lower insulin resistance, serum triglyceride, and SBP and higher adiponectin concentrations among patients with metabolic syndrome in highest quartiles of DDS. Moreover, patients with the CC genotype were more likely to have higher BMI, fasting blood glucose, AST, and ALT. This significant interaction gives a possible evidence of a VEGFA-DDS association that may be relevant to metabolic syndrome. Further studies are warranted to clarify the underlying mechanisms of these interactions.

Keywords: Dietary diversity score; MMP-3; Metabolic syndrome; VEGFA.