Preeclampsia is one of the most severe gestational complications which is one
of the leading causes of maternal and perinatal morbidity and mortality. A
growth in the incidence of severe and combined forms of the pathology has been
observed in recent years. According to modern concepts, inadequate
cytotrophoblast invasion into the spiral arteries of the uterus and development
of the ischemia-reperfusion syndrome in the placental tissue play the leading
role in the development of preeclampsia, which is characterized by
multipleorgan failure. In this regard, our work was aimed at studying the
patterns of placental tissue transcriptome that are specific to females with PE
and with physiological pregnancy, as well as identifying the potential
promising biomarkers and molecular mechanisms of this pathology. We have
identified 63 genes whose expression proved to differ significantly in the
placental tissue of females with PE and with physiological pregnancy. A cluster
of differentially expressed genes (DEG) whose expression level is increased in
patients with preeclampsia includes not only the known candidate genes that
have been identified in many other genome-wide studies (e.g.,
LEP, BHLHB2, SIGLEC6,
RDH13, BCL6), but also new genes
(ANKRD37, SYDE1, CYBA,
ITGB2, etc.), which can be considered as new biological
markers of preeclampsia and are of further interest. The results of a
functional annotation of DEG show that the development of preeclampsia may be
related to a stress response, immune processes, the regulation of cell-cell
interactions, intracellular signaling cascades, etc. In addition, the features
of the differential gene expression depending on preeclampsia severity were
revealed. We have found evidence of the important role of the molecular
mechanisms responsible for the failure of immunological tolerance and
initiation of the pro-inflammatory cascade in the development of severe
preeclampsia. The results obtained elaborate the concept of the pathophysiology
of preeclampsia and contain the information necessary to work out measures for
targeted therapy of this disease. ;
Purpose The role of genetic polymorphisms in the pathogenesis of recurrent pregnancy loss (RPL) has been studied intensively. Complex diseases, including miscarriage, are believed to have a polygenic basis, and gene-gene interactions can play a significant role in the etiology of the disease. This study was conducted to investigate the association of gene-gene interactions with angiogenesis, endothelial dysfunction-related gene polymorphisms, and RPL. Methods A case-control study was conducted with 253 unrelated RPL patients with 2 or more spontaneous pregnancy losses and 339 healthy women with no history of pregnancy complications. Genotyping of single-nucleotide polymorphisms (SNPs) was performed using real-time polymerase chain reaction (real-time PCR), restriction fragment length polymorphism (RFLP), or allele-specific polymerase chain reaction methods. Results The genotypes 677TT of the MTHFR gene, 936TT, 936CT, and 634CC, 634GC of the VEGF gene, and allele 894T of the NOS3 gene were associated with a predisposition to RPL in the Russian population. A significant role of additive and epistatic effects in the gene-gene interactions of the SNPs of SERPINE-1, ACE, NOS3, MTHFR, and VEGF genes in RPL was demonstrated. Conclusions The results showed that gene-gene interactions are important for RPL susceptibility. Additionally, analysis of the genotype combinations of several allelic variants provides more information on RPL risk than analysis of independent polymorphic markers.
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