Association of vascular endothelial growth factor A polymorphisms and aberrant expression of connexin 43 and VEGFA with idiopathic recurrent spontaneous miscarriage.

Abstract

Idiopathic recurrent spontaneous miscarriage (IRSM) is one of the pregnancy outcomes that affects 1-2% of women trying to conceive. Specific genotype or aberrant expression of vascular endothelial growth factor A (VEGFA) and connexin 43 (Cx43) as two important genes for embryonic development are deemed to increase the risk of IRSM. To investigate any possible association of VEGFA polymorphisms and aberrant expression of Cx43 and VEGFA with IRSM, we carried out a case-control study including embryo chorionic villus tissues of 100 pregnant women with IRSM and 100 embryo chorionic villus tissues of healthy pregnant women without history of miscarriage. Restriction fragment length polymorphism was used for genotyping of rs699947 (-2578C/A) and rs2010963 (-634G/C) polymorphisms in VEGFA. Besides, quantitative real-time PCR was performed for VEGFA and Cx43 expression analysis. The results showed that the frequency of -634G/C and C/C genotypes was significantly higher in aborted fetuses (P = 0.001 and P < 0.001, respectively) compared to the control group's. However, the frequency of -2578C/A genotypes was not significantly different between the cases and controls. Moreover, a significant higher expression of VEGF (P = 0.0005) and Cx43 (P = 0.0011) was observed in chorionic villus tissues of women with IRSM. The finding demonstrated that IRSM frequency may depend on GC and CC genotypes of rs2010963 VEGF polymorphism and expression level of VEGF and Cx43 in IRSM patients was increased.