Genetic variation in vascular endothelial growth factor gene and its association with recurrent spontaneous abortion.

Abstract

Vascular endothelial growth factor (VEGF) plays a main role in fetal and placental angiogenesis and is secreted by different cells of endometrium and placenta. In the present study we investigated the association of VEGF gene polymorphisms with recurrent spontaneous abortion (RSA). A case-control study of 100 women with at least two consecutive pregnancy losses before 20 weeks of gestational age and 100 fertile controls was performed to evaluate four VEGF gene polymorphisms including +936C/T (rs3025039), -154G>A (rs1570360), rs3025010 and +5092A/C (rs2146323). Genotyping was performed by PCR based restriction fragment length polymorphism (PCR-RFLP) analysis. Haplotype frequency was estimated for three SNPs' genotypes. Analysis of genetic STRUCTURE and K means clustering were performed to estimate genetic variation. We found an association between -154G/A heterozygous genotype (GA) and RSA. The VEGF single nucleotide polymorphism (SNP) in intron region (rs3025010) in different inheritance models was also associated with RSA. Linkage disequilibrium analysis revealed that VEGF SNP in intron 5 (rs3025010) was linked to promoter region SNP (rs1570360). Cluster analysis including Neighbor Joining and K-means clustering supported genetic differentiation of women with RSA and controls. Allelic polymorphisms in common VEGF SNPs was associated with RSA samples and haplotypes with at least one minor allele showing an association with RSA pathogenesis (Tab. 8, Fig. 2, Ref. 35).