Conclusion
This study exposed twenty significant CpG sites linking DNA methylation to VEGF-A concentration. Methylation detected in promoter regions, such as TPX2 and HAS-1, could explain previously reported associations with the VEGFA gene. Methylation may also help in the understanding of the regulatory mechanisms of other genes located in the vicinity of detected CpG sites.
Methods
VEGF-A concentrations of healthy participants from the STANISLAS Family Study (n = 201) were comprehensively assessed for association with DNA methylation. Genome-wide DNA methylation profiles were determined in whole blood DNA using the 450K Infinium BeadChip Array (Illumina). VEGF-A concentration in PBMC extracts was detected using a high-sensitivity multiplex Cytokine Array (Randox Laboratories, UK).
Results
Epigenome-wide association analysis identified 41 methylation sites significantly associated with VEGF-A concentrations derived from PBMC extracts. Twenty CpG sites within 13 chromosomes reached Holm-Bonferroni significance. Significant values ranged from P = 1.08 × 10-7 to P = 5.64 × 10-15.