Abstract
Numerous studies have examined the genetic association of vascular endothelial growth factor (VEGF) single nucleotide polymorphisms (SNPs) with recurrent pregnancy loss (RPL). However, of the four known SNPs in the 3′-untranslated region (3′-UTR) of VEGF, three SNPs—namely rs3025040 (1451C>T), rs10434 (1612G>A), and rs3025053 (1725G>A)—remain poorly characterized with regard to RPL. Herein, we evaluated the association between these three SNPs in the VEGF 3′-UTR and RPL susceptibility. We analyzed VEGF 3′-UTR gene variants in with and without RPL using TaqMan allelic discrimination. There were significant differences in the genotype frequencies of 1612G>A (GA: adjusted odds ratio (AOR), 0.652; 95% confidence interval (CI), 0.447–0.951; p = 0.026) and 1725G>A (GA: AOR, 0.503; 95% CI, 0.229–0.848; p = 0.010) in RPL patients vs. controls. Our results indicate that the 1612G>A and 1725G>A polymorphisms in the 3′-UTR of VEGF are associated with RPL susceptibility in Korean women. These data suggest that VEGF 3′-UTR polymorphisms may be utilized as biomarkers for the detection of RPL risk and prevention.
Highlights
Recurrent pregnancy loss (RPL) is commonly defined as more than two consecutive miscarriages prior to 20 weeks [1], the American Society for Reproductive Medicine has expanded its definition to include two consecutive losses [2]
We found that two single nucleotide polymorphisms (SNPs) combinations were associated with RPL: 1451CC/1725GA (AOR, 0.510; 95% confidence interval (CI), 0.290–0.898; p = 0.020), and 1612GA/1725GA (AOR, 0.472; 95% confidence intervals (95% CIs), 0.258–0.866; p = 0.015)
We investigated the association between three SNPs in the 3 -untranslated region (3 -UTR) of the vascular endothelial growth factor (VEGF) gene, namely 1451C>T, 1612G>A, and 1725G>A, and the prevalence of RPL in Korean women
Summary
Recurrent pregnancy loss (RPL) is commonly defined as more than two consecutive miscarriages prior to 20 weeks [1], the American Society for Reproductive Medicine has expanded its definition to include two consecutive losses [2]. RPL is experienced by approximately 2–4% of reproductive-age women, a considerable number, and is morally devastating for couples who wish to become pregnant, RPL is often disappointing for clinicians. No diagnostic factors have been identified that distinguish RPL patients that have suffered different numbers of pregnancy losses [3]. RPL etiology remains unclear [4], the causes of RPL are known to include anatomic factors, hormonal, and metabolic factors, and antiphospholipid syndrome. The VEGF-A gene encompasses 14 kb on human chromosome 6 and has eight exons [5]
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