Title : Interlocus interactions of the ESR1 gene are associated with preeclampsia
Abstract:
The aim of the study was to detect the interlocus interactions of the ESR1 gene associated with preeclampsia (PreE). Material and methods. The sample volume totaled 514 pregnant women, of which 190 had PreE and 324 individuals were with the physiological course of pregnancy. The examination of pregnant women was carried out in the Perinatal Center of the St. Joasaph Regional Clinical Hospital in Belgorod. Genotyping of three polymorphisms of the ESR1 gene (rs9340799,rs2234693, rs3798577) was performed. Associations of polymorphisms with PreE were evaluated in the PLINK program using the logistic regression method. Results. Polymorphisms rs9340799,rs2234693, rs3798577 of the ESR1 gene were not independently associated with PreE. However, epistatic interaction of two loci - rs9340799 and rs3798577, reduced the risk of PreE (odds ratio 0.56, p=0.004/pbonf=0.012). These polymorphisms and six SNPs strongly linked to rs9340799 (r2≥0.8) have significant functional effects: they affect the interaction of DNA with three regulatory proteins (NRSF/SIN3AK20/TCF12) and more than twenty transcription factors such as Foxo, Foxa, Foxf2, Foxd1, Foxj1, HDAC2, Foxk, Sox, p300, TCF12, etc.; they are located in the region of modified histones marking enhancers and promoters, the region of hypersensitivity to DNase 1 in more than thirty different organs (tissues) involved in the biology of PreE. Conclusion. The interlocus interaction of two ESR1 gene polymorphisms (rs9340799 and rs3798577) is associated with PreE.
