Association of Growth Factors Genes with Miscarriage

The study was aimed to investigate the association of VEGFA gene polymorphic variants -2578C>A (rs699947) and -634G>C (rs2010963) and TGFB1 gene 915G>C (rs1800471) and gene expression level with miscarriage in the first trimester.

288 women with different courses of pregnancy and 61 chorionic tissue samples were involved in case-control study. Allele-specific polymerase chain reaction in real time was used for genotyping. Next, gene-gene interactions were analyzed using the multifactor dimensionality reduction method. VEGFA and TGFB1 genes expression levels were determined by RT-PCR.

It was found that SNP rs699947 was associated with the miscarriage risk change (p=0.05). The CC genotype was associated with reduced risk of abortion in the first trimester, and the CA genotype with increased risk. Genotypes VEGFA -2578CC/VEGFA -634CG, VEGFA -2578AA/VEGFA -634CG,and VEGFA -2578CC/ VEGFA -634CG/TGFB1 936CC were associated with lowered risk of miscarriage in the first trimester. mRNA level of TGFB1 was significantly higher in decidual tissue compared to chorionic tissue in normally progressing pregnancy (p=0.003). VEGFA gene expression level was directly correlated with the TGFB1 mRNA level (R=0.60; p=0.038). In pregnancy loss, an inverse relationship was observed (R=-0.76; p=0.028).

The SNP rs699947 is associated with pregnancy loss in the first trimester. The MDR analysis data showed the significant relationship between VEGFA and TGFB1 genes in two-locus and three-locus models. A change in the ratio of the concentrations of growth factors can disrupt the processes of cell division, apoptosis and angiogenesis processes.