Association between SNPs of Circulating Vascular Endothelial Growth Factor Levels, Hypercholesterolemia and Metabolic...

Four single nucleotide polymorphisms (SNPs); rs6921438 and rs4416670 in LOC100132354-C6orf223, rs6993770 in ZFPM2, and rs10738760 in VLDLR-KCNV2 were reported to explain up to 50% of the heritability of vascular endothelial growth factor circulating levels. These SNPs were also studied for possible associations with circulating lipid levels in supposedly healthy European individuals and in a limited number of Iranian individuals with metabolic syndrome. To go further, the association of those four SNPs with plasma lipid parameters, hypercholesterolemia and metabolic syndrome (MetS) was assessed.

A cross-sectional study was conducted on 460 individuals chosen from the general population. Demographic and clinical data were collected and DNA was extracted and genotyped using Kompetitive allele specific PCR (KASP™). A meta-analysis followed, combining our participants with the Iranian individuals (n = 336).

Whereas rs10738760 was associated with total cholesterol (Tchol) (p = 0.01), rs6993770 showed significant associations with both Tchol and low-density lipoprotein cholesterol (LDL-C) levels (p = 0.007 and p = 0.01 respectively). Using a multivariate logistic regression model adjusted for different confounding factors, we found that rs6993770 was associated with hypercholesterolemia, specifically high Tchol (p = 0.01) and LDL-C levels (p = 0.01). Furthermore, rs10738760 was positively associated with the risk of MetS in these individuals (p = 0.02) and in the meta-analysis (OR = 1.67, p = 0.01).

Our results suggest that whereas rs6993770 in ZFPM2 was positively associated with hypercholesterolemia, rs10738760 (VLDLR-KCNV2) has a possible implication in MetS in two Middle Eastern populations.