Associations of VEGF-A-Related Variants with Adolescent Cardiometabolic and Dietary Parameters

Abstract

Previous research has allowed the identification of variants related to the vascular endothelial growth factor-A (VEGF-A) and their association with anthropometric, lipidemic and glycemic indices. The present study examined potential relations between key VEGF-A-related single-nucleotide polymorphisms (SNPs), cardiometabolic parameters and dietary habits in an adolescent cohort. Cross-sectional analyses were conducted using baseline data from 766 participants of the Greek TEENAGE study. Eleven VEGF-A-related SNPs were examined for associations with cardiometabolic indices through multivariate linear regressions after adjusting for confounding factors. A 9-SNP unweighted genetic risk score (uGRS) for increased VEGF-A levels was constructed to examine associations and the effect of its interactions with previously extracted dietary patterns for the cohort. Two variants (rs4416670, rs7043199) displayed significant associations (p-values < 0.005) with the logarithms of systolic and diastolic blood pressure (logSBP and logDBP). The uGRS was significantly associated with higher values of the logarithm of Body Mass Index (logBMI) and logSBP (p-values < 0.05). Interactions between the uGRS and specific dietary patterns were related to higher logDBP and logGlucose (p-values < 0.01). The present analyses constitute the first-ever attempt to investigate the influence of VEGF-A-related variants on teenage cardiometabolic determinants, unveiling several associations and the modifying effect of diet.

Variation in VEGFA and risk of cardiovascular disease in the UK Biobank

“…Thus, by utilizing a lipid genetic score constructed from genetic variations associated with VEGFA, our study extended its inquiry, shedding light on a causal link between lipid metabolism and CVD risk. Previous research has firmly established the additional CVD risk associated with pathogenic FH variations (64)(65)(66). Currently, statins, ezetimibe, bile acid sequestrants, and PCSK9 inhibitors are used as standard agents for lipid-lowering interventions.…”

Dietary Patterns, Food Intake and Health: New Evidence from Epidemiological and Genetic Studies

“…Notably, these genes have a gene-by-environment phenomenon, i.e., they can only proxy alcohol intake among ever drinkers but would not work among never drinkers [14]. Kafyra et al examined the interactions between vascular endothelial growth factor A (VEGFA) gene and dietary patterns, and explored their associations with cardiometabolic factors among 766 participants in Greek TEENAGE study [15]. Gene-byenvironment MR has been further developed to use offspring genotypes as proxies for unmeasured maternal genotypes, in order to explore offspring intrauterine exposures on their later life outcomes [16].…”

Atherosclerosis, Diabetes Mellitus, and Cancer: Common Epidemiology, Shared Mechanisms, and Future Management

“…VEGF is part of the classical angiogenic factors that mediate atherosclerotic angiogenesis, in addition to its role in neovascularization, plaque growth/progression, and instability [25]. VEGF has a multifactorial influence on energy homeostasis, the lipidemic profile, insulin resistance, glucose sensitivity, and cardiac function [189]. The effects of VEGFs on the development of atherosclerosis are complex and diverse, but VEGF-A prevents the repair of endothelial damage, contributing to atherogenesis and promoting monocyte adhesion, transendothelial migration, and activation [188].…”