Analysis of VEGFA Variants and Changes in VEGF Levels Underscores the Contribution of VEGF to Polycystic Ovary Syndrome

Abstract

BackgroundVascular 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.AimTo evaluate the association of altered VEGF levels, stemming from the presence of specific VEGFA variants, with altered risk of PCOS.Subjects and MethodsRetrospective 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.ResultsAmong 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.ConclusionThis 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.

Effects of melatonin on the synthesis of estradiol and gene expression in pig granulosa cells

“…VEGFɑ could promote estradiol synthesis and survival of GCs in buffalo . SNP analysis revealed that VEGFɑ was associated with PCOS in humans . These results indicate that CDK6 , FILIP1L , ACAT2 , CEBPD , and VEGFɑ all have important functions in ovaries.…”

Association between vascular endothelial growth factor gene polymorphisms and PCOS risk: a meta-analysis

“…Five case-control studies involving 895 women with PCOS and 907 controls were included to estimate the relationship between the VEGF +405G>C (rs2010963) polymorphism and PCOS risk (Almawi et al, 2016;Guruvaiah et al, 2014;Huang et al, 2019;Lee et al, 2008;Vural et al, 2009). Overall, the pooled analysis showed no significant association between +405G>C (rs2010963) and PCOS in five genetic models.…”

“…Full texts of the remaining nine were obtained and studied, and two of them were further excluded because of the absence of genotypic data. In the end, seven studies with detailed genotypic data were included in the systemic review (Almawi et al, 2016;Ben Salem et al, 2016;Gomes et al, 2019;Guruvaiah et al, 2014;Huang et al, 2019;Lee et al, 2008;Vural et al, 2009). These selected studies involved 1100 patients with PCOS and 1141 control individuals.…”

“…Given the reported association between VEGF expression and PCOS, several studies (Almawi et al, 2016;Ben Salem et al, 2016;Gomes et al, 2019;Guruvaiah et al, 2014;Huang et al, 2019;Lee et al, 2008;Vural et al, 2009) have been performed to evaluate the role of VEGF SNP in the risk of PCOS. However, to date, the role of VEGF SNP in the regulation of PCOS pathogenesis remains unclear.…”

Association between VEGF gene polymorphisms (11 sites) and polycystic ovary syndrome risk

“…However, the results were not conclusive or consistent. Considering the vital role of VEGF gene in the development of PCOS, we conducted a timely meta-analysis including 11 SNPs [21][22][23][24][25][26][27][28][29] to derive a more comprehensive estimation of the association between VEGF gene polymorphisms and PCOS susceptibility to identify some significant biomarkers.…”