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EVOLUTIONARY-GENETIC ANALYSIS OF THE ROLE OF REGULATORY REGIONS IN CORO2A GENE IN THE DEVELOPMENT OF HEREDITARY PREDISPOSITION TO PREECLAMPSIA IN RUSSIAN AND YAKUT ETHNIC GROUPS

Background: Preeclampsia (PE) is one of the most serious pregnancy complications and is the leading cause of maternal and perinatal morbidity and mortality, because there are currently no prognostic biomarkers and effective pharmacological therapy of PE, and the etiopathogenesis of this pathology remains poorly understood. Therefore, studying the genetics components of PE is a promising approach. The aim of the study: To study PE genetics components via the regulatory polymorphic variants (rSNPs) of the new CORO2A candidate gene and to detect the role of natural selection in its formation. Materials and methods: We analyzed 925 DNA samples of women from two ethnic groups: Russian and Yakut (a group of patients with PE, N=412 women and a control group, N=513 women). The search of rSNPs was conducted using the online resource «RegulomeDB». Genotyping was performed using MALDI-TOF mass-spectrometry. Chi-square or Fisher's exact tests were used to compare the frequencies of alleles and genotypes between the analyzed groups. We used the INSIGHT method to detect the signals of natural selection in the evolutionary line of parvorder Catarrhini. Results: In the Russian population, for the allele C of regulatory polymorphism variant rs10985257 has been shown to associate with preeclampsia (p=0.005, OR=2.33, CI:1.32-4.11), while the allele A (p=0.005, OR=0.43, CI:0.24-0.76) and genotype AA (p=0.02, OR=0.45, CI:0.24-0.85) have protective properties. In the evolutionary line of parvorder Catarrhini we demonstrated the effect of weak negative selection for rs10985257, rs2231656 and rs78486797. Conclusions: We demonstrated a significant role of the rs10985257 and adaptive changes of this rSNP at the macroevolutionary level in the formation of hereditary predisposition to PE.

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