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Implications of VEGF gene sequence variations and its expression in recurrent pregnancy loss

Published:August 20, 2021DOI:https://doi.org/10.1016/j.rbmo.2021.08.009

      Abstract

      Research question

      What is the association between VEGF gene sequence variants and its mRNA expression in recurrent pregnancy loss (RPL)? Vascular endothelial growth factor (VEGF) has a prominent role in pregnancy and affects pregnancy outcome. The association of VEGF gene 1154G>A, 634G>C and 583C>T polymorphic variations with cases of RPL and full-term fertile women as controls was investigated.

      Design

      Two hundred women with RPL and 240 women healthy controls were included. The restriction fragment length polymorphism method was used for genotyping and quantitative real-time polymerase chain reaction was used for analysis of mRNA expression.

      Results

      In VEGF 1154G>A, significant differences were found in homozygous AA genotype between case and control participants. The variant allele A frequency was significantly more abundant in RPL cases (0.41) than controls (0.19) (P < 0.0001). Only RPL cases with the multi-generation family history of miscarriages and those without any history showed significant differences of combined genotype GA+AA (P < 0.0001). In VEGF 634 G>C, CC genotype and allele C showed significantly increased frequency in RPL cases compared with healthy controls (P < 0.0001). The association between VEGF-1154 G>A SNP and VEGF-A mRNA expression levels was significant in RPL cases (P = 0.004). Also in VEGF-583 C>T, CT genotypes were seen significantly associated with cases (P = 0.003). The heterozygous genotype GA was significantly (P = 0.03) associated with upregulation and downregulation of VEGF mRNA, whereas the homozygous variant genotype AA only leads to low expression levels of VEGF mRNA in patients with RPL.

      Conclusions

      All the variants of VEGF play a vital role in an increased susceptibility to RPL. Also, VEGF-1154, AA genotypes are associated with its altered low mRNA expression in women with RPL and seem to affect pregnancy outcome.

      KEYWORDS

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      Biography

      Ina Amin is a doctoral researcher at the Department of Clinical Biochemistry, University of Kashmir Srinagar, Kashmir, India. She is currently undertaking research on the prominent genetic and cytogenetic causes of pregnancy losses at the Advanced Centre for Human Genetics, Sheri Kashmir Institute of Medical Sciences Soura Srinagar.
      Key message
      Studies of the VEGF gene genetic linkage enable a better understanding of normal occurrences in early pregnancy and the aetiology of recurrent pregnancy loss (RPL). Maternal polymorphism variations of VEGF-1154G>A, -634G>C and 583C>T were identified as having a strong effect on the risk of pregnancy and a predisposition to RPL.