Data from: Analysis of VEGFA variants and changes in VEGF levels underscores the contribution of VEGF to polycystic ovary syndrome

Background. Vascular endothelial growth factor (VEGF) contributes to the
pathogenesis of polycystic ovary syndrome (PCOS), and genetic variations
in VEGFA gene were suggested to contribute to VEGF secretion and PCOS.
Aim. To evaluate the association of altered VEGF levels, stemming from the
presence of specific VEGFA variants, with altered risk of PCOS. Subjects
and Methods. Retrospective case-control study, performed between
2012-2015. Study subjects comprised 382 women with PCOS, and 393 control
subjects. ELISA measured VEGF levels; genotyping of VEGFA variants was
done by allelic exclusion. Results. Among the 12 tested VEGFA SNPs, minor
allele frequency of only rs3025020 was significantly higher in PCOS cases
than control women. Increased and reduced PCOS risk was seen with
rs3025020 and rs2010963 genotypes, respectively. Increases and reduction
in VEGF levels were associated with rs3025020 and rs2010963, respectively.
Increased fasting insulin and HOMA-IR, and bioactive testosterone were
linked with rs3025020, while carriage of rs2010963 was linked with
reduction in fasting insulin, and free and bioactive testosterone. Of the
12 VEGFA variants, 9 were in LD, thus allowing construction of 9-locus
haplotypes. Increased frequency of CAACAGCGA haplotype was seen in PCOS
cases, after controlling for BMI, free and bioactive testosterone, SHBG,
free insulin and HOMA-IR. Conclusion. This study confirms the contribution
of altered VEGF secretion, resulting from genetic variation in VEGFA gene
into the pathogenesis of PCOS. This supports a role for VEGF as PCOS
candidate locus.