Association of genetic polymorphisms in VEGF -460, -7 and -583 and hematocrit level with the development of idiopathic recurrent pregnancy loss and a meta-analysis.

Abstract

The present study was performed to investigate whether genetic variants of VEGF are associated with recurrent pregnancy loss (RPL) in Korean women and to provide insight into the role of VEGF in the pathogenesis of RPL development. A cohort of 384 women with idiopathic RPL with a history of two or more uxexplained consecutive early pregnancy losses and 236 control women were recruited from an infertility center of university-teaching hospital in Korea between March 1999 and February 2010. We examined three VEGF polymorphisms (rs833061, rs3025020 and rs25648). Genotyping was assessed by polymerase chain reaction (PCR)-restriction fragment length polymorphism analyses (rs3025020) or real-time PCR (rs833061, rs25648). There was no statistically significant difference in frequency of each three VEGF polymorphic loci between the control and RPL groups. Allele combinations of VEGF rs3025020/rs833061 TT/TC and TT/TC+CC genotypes were associated with an increased frequency of RPL development [odds ratio (OR)=3.525, 95% confidence interval (CI)=1.154-10.767, p=0.027 and OR=3.815, 95% CI=1.256-11.588, p=0.018, respectively]. Haplotype analysis revealed that two allele combinations (rs833061/rs3025020 C-T and rs25648/rs3025020 T-T) were associated with an increased prevalence of RPL (OR=2.548, 95% CI=1.502-4.320, p=0.0004 and OR=16.50, 95% CI=0.976-278.8, p=0.003, respectively). Allele combinations and haplotypes of rs3025020/rs833061 were associated with maternal blood hematocrit (HCT) levels in the RPL group (p=0.048 and 0.006, respectively). The VEGF rs833061/rs3025020 genotype allele was related to the development of RPL and was also associated with maternal blood HCT levels in RPL patients. However, further studies are needed to clarify the exact mechanism of how VEGF and HCT are involved in RPL development.