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Vol 50(2016) N 5 p. 768-776; DOI 10.1134/S0026893316050162 Full Text

V.N. Serebrova1*, E.A. Trifonova1,2, T.V. Gabidulina3, I.Yu. Bukharina3, T.A. Agarkova3, I.D. Evtushenko4, N.R. Maksimova5, V.A. Stepanov1,2

Detection of novel genetic markers of susceptibility to preeclampsia based on an analysis of the regulatory genes in the placental tissue

1Research Institute of Medical Genetics, Tomsk, 634050 Russia
2National Research Tomsk State University, Tomsk, 634050 Russia
3The Institute for Obstetrics and Gynecology, Tomsk, 634063 Russia
4Regional Perinatal Center, Tomsk, 634063Russia
5Laboratory of Genome Medicine, Clinics of Medical Institute, North East Federal University, Yakutsk, 677019 Russia

*vika.serebrova@medgenetics.ru
Received - 2015-12-14; Accepted - 2016-03-18

Regulatory single nucleotide polymorphisms (rSNPs) are the least-studied group of SNP; however, they play an essential role in the development of human pathology by altering the level of candidate genes expression. In this work, we analyzed 29 rSNPs in 17 new candidate genes associated with preeclampsia (PE) according to the analysis of the transcriptome in placental tissue. Three ethnic groups have been studied (yakut, russian, and buryat). We have detected significant associations of PE with eight rSNPs in six differentially expressed genes, i.e., rs10423795 in the LHB gene; rs3771787 in the HK2 gene; rs72959687 in the INHA gene; rs12678229, rs2227262, and rs3802252 in the NDRG1 gene; rs34845949 in the SASH1 gene; and rs66707428 in the PPP1R12C gene. We used a new approach to detecting genetic markers of multifactorial diseases in the case of PE based on a combination of genomic, transcriptomic, and bioinformatic approaches. This approach proved its efficiency and may be applied to detecting new potential genetic markers in genes involved in disease pathogenesis, which reduces missing heritability in multifactorial diseases.

preeclampsia, association study, genetic markers, Russian population, regulatory single-nucleotide polymorphisms (rSNPs), placenta, transcriptome



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