The VEGF +405 G>C 5' untranslated region polymorphism and risk of PCOS: a study in the South Indian Women

Abstract

Purpose The aim of this study was to investigate the association between two common single nucleotide polymorphisms (SNPs) in the vascular endothelial growth factor (VEGF) gene (−460C/T and +405G/C) and polycystic ovary syndrome (PCOS) risk in south Indian women. Methods This study involves clinically confirmed PCOS patients (n=126) and non-PCOS controls (n=130) of south Indian origin (Dravidian linguistic group). Genotyping of the VEGF gene −460C/T and +405G/C SNPs were performed by PCR and sequencing analysis. Haplotype frequencies for multiple loci and the standardized disequilibrium coefficient (D') for pairwise linkage disequilibrium (LD) were assessed by Haploview Software. Results The frequencies of +405G/G genotype (P=0.03) and +405G alleles (P=0.006) were significantly higher in patients compared to controls. Whereas the genotype and allele frequencies of −460C/T SNP were not significantly different between patients and controls. In addition, LD analysis revealed no significant difference between patients and controls. Conclusion Our findings suggest that the VEGF +405G/C polymorphism may constitute an inheritable risk factor for PCOS in south Indian women.

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

“…PCOS diagnosis was based on the 2003 Rotterdam Criteria, which allows for inclusion of ultrasound examination findings [12, 27]. By comparison to previous related studies, mean BMI was higher in the studied population, similar to the study on South Indian women [20], but different from Korean [28] and Turkish [19] studies, which involved lean PCOS cases and control women. This in turn translated into lower testosterone and insulin compared to our study [19, 28].…”

“…The association between VEGFA gene polymorphisms and PCOS was reported for Korean [28], Turkish [19], and South Indian [20] populations, but with mixed outcome. This was attributed to diversity in sample size, ethnic origin of participants, study designs, diagnostic criteria of PCOS, and statistical methods.…”

“…This was attributed to diversity in sample size, ethnic origin of participants, study designs, diagnostic criteria of PCOS, and statistical methods. Neither rs833061 [19, 20] nor rs699947 [19] were significantly associated with PCOS among Turkish [19] and South Indian [20] women. While none of the 10 “common” VEGFA variants was associated with PCOS in Koreans, the study of Lee on 134 Korean women with PCOS and control women identified +13553C/T ( P = 0.033) and +9812 C/T ( P = 0.044) to be negatively associated with PCOS [28].…”

“…This suggests a possible susceptible and protective nature of these variants, respectively. The lack of association of the other variants, including rs833061 (-460T/C), rs699947 (-2578C/A), and rs1570360 (-1154G/A), were reminiscent of Korean [28], Turkish [19], and South Indian [20] studies. While not tested for its possible association with PCOS, rs3025020 (-583T>C) was previously linked with increased risk of recurrent pregnancy loss in Bahraini [24] and Chinese [25] women.…”

“…Two studies conducted on Turkish [19] and South Indian [20] cohort revealed no association between -2578C/A and -460T/C VEGFA SNPs and PCOS. Other studies that investigated the association between VEGFA SNPs and adverse pregnancy outcomes, such as ovarian hyperstimulation syndrome, ovarian cancer [21], pre-eclampsia [22, 23], spontaneous miscarriage [24, 25], and cervical cancer [26] yielded mixed results.…”