The role of VEGFA in regulation of fat distribution

Background: Body fat distribution as one of the main predictors of obesity associated complication is controlled by genetic factors. Polymorphisms in the vascular endothelial growth factor A (VEGFA) have been shown to be associated with waist to hip ratio (WHR) in recent genome-wide association studies. We tested the hypothesis that VEGFA is involved in the control of fat distribution and its expression correlates with obesity related traits.

Material and methods: We measured the mRNA levels of VEGFA in paired human samples of visceral and subcutaneous adipose tissue from 570 individuals with detailed metabolic testing. VEGFA serum levels were measured in a second independent cohort (Sorbs from Germany; N = 1000). Previously reported single nucleotide polymorphisms (SNPs) rs1358980 and rs6905288 associated with WHR were genotyped in all subjects. We conducted correlation analyses, eQTL and genetic association studies.

Results: The mRNA expression of VEGFA was significantly higher in visceral adipose tissue vs. subcutaneous adipose tissue (p< 0.001). In addition the mRNA levels correlated with % body fat (p< 0.05, adjusted for sex and age) and waist (adj. p< 0.001). Rs1358980 was associated with waist and hip and both SNPs exhibited association with traits of the lipid metabolism (total and LDL cholesterol; adj. p< 0.05).

Finally, eQTLs were found for rs1358980 (adj. p< 0.01) and rs6905288 (adj. p< 0.05) in visceral adipose tissue.

Conclusion: Our data support the involvement of VEGFA in regulation of fat distribution. The observed eQTLs suggest that SNP associations with WHR might be mediated by their effects on mRNA expression.