ANXA5 and VEGFA Gene Variants in Women with Early Pregnancy Losses from North Macedonia.

Early pregnancy loss (EPL) is the most common pregnancy complication, found in approximately 15% of all clinically recognized pregnancy complications. Up to date, various maternal as well as fetal factors are reported as a cause of EPLs. However, in approximately 50% of EPL cases, the exact cause is not clearly identified and these cases are referred as idiopathic. The aim of our study was to examine the association of four distinct variants in the ANXA5 gene and two variants within the VEGFA gene in a cohort of women with EPLs from North Macedonia. This group was compared to a control group of women matched by ethnic background without pregnancy loss and at least one live birth. We also aimed to establish an effective and cost-efficient method for their detection based on multiplex single-base extension. Among 190 women experiencing EPLs, and 190 samples from women without a history of pregnancy loss (control group), our results demonstrated a statistically significant prevalence of heterozygotes for the M2/ANXA5 haplotype in women with EPLs, compared to the control group (p=0.0006). In the analyses comparing genotypic frequencies for the variants in the VEGFA gene, higher frequencies were generally observed among women experiencing EPLs, however without statistical significance. Our study aligns with multiple studies showing that M2 and M1 ANXA5 haplotypes are more prevalent in patients with pregnancy loss and presents an affordable genotyping technique for the specific ANXA5 and VEGFA variants.