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The associations of genes differentially expressed in the placenta with the risk of preeclampsia in women in Central Russia were studied. The study was conducted on a sample of 366 pregnant women with preeclampsia and 631 women in the control group. All pregnant women underwent typing of nine specially selected SNPs of genes differentially expressed in the placenta. Associations of SNPs of candidate genes with preeclampsia were assessed using logistic regression. For polymorphisms that showed associations with PE, their functional effects were assessed in silico. It was established that the G allele rs36011588 TMEM136 was a protective factor (OR = 0.65), and the CA haplotype of the rs2532058–rs66707428 PPP1R12C was a risk factor (OR = 1.21) for the development of preeclampsia. The associations of these SNPs with developing preeclampsia may be due to their important epigenetic significance: they are located at the sites of modified histones in the regions of promoters and enhancers, in DNase-hypersensitive sites, in binding sites for regulatory proteins, and in the binding domains for transcription factors. Also, these loci are associated with the level of transcription and alternative splicing in tissues pathogenetically significant for the development of preeclampsia. [ABSTRACT FROM AUTHOR]

The associations of single nucleotide polymorphisms of the LHCGR gene with the formation of endometrial hyperplasia in the Russian population were studied. Genotyping of four loci of the LHCGR gene (rs4953616, rs4374421, rs6729809, rs7579411) was performed in 520 patients with endometrial hyperplasia (EH) and 981 women of the control group. A significant contribution to the susceptibility to endometrial hyperplasia of the rs7579411 polymorphism of the LHCGR gene has been established. The genotype C/C rs7579411 of the LHCGR gene is risky for EH (OR = 1.26, p = 0.05), whereas the allelic variant T rs7579411 of the LHCGR gene is a protective factor for EH (OR = 0.79, pperm = 0.05). The rs7579411 locus of the LHCGR gene has significant epigenetic effects (located in DNA regions marking regulatory sequences (enhancers)) and is associated with the expression of the STON1-GTF2A1L gene in organs and tissues (thyroid gland, peripheral blood) involved in the pathophysiology of the disease. At the same time, the allele T rs7579411 of the LHCGR gene is associated with low transcriptional activity of the STON1-GTF2A1L gene (β = –0.25). [ABSTRACT FROM AUTHOR]

A replicative study of associations of the LOXL1 gene polymorphism with primary open-angle glaucoma (POAG) in the female population of the Central Chernozem region of Russia was performed. The work was done in the design "patients–control." The study sample consisted of 290 women with POAG and 220 women in the control group. Three polymorphic loci of the LOXL1 gene (rs2165241, rs4886776, rs893818) were genotyped by PCR (Tag-Man probe technology). The study revealed that SNPs of the LOXL1 gene (rs2165241, rs4886776, rs893818) are associated with POAG in women of the Central Chernozem region of Russia: allele C of rs2165241 (OR = 0.33–0.45 at pperm ≤ 0.0005), alleles A of rs4886776 (OR = 0.62–0.63 at pperm ≤ 0.031) and rs893818 (OR = 0.53–0.62 at pperm ≤ 0.007), and the CAA haplotype of rs2165241–rs4886776–rs893818 (OR = 0.56 at pperm = 0.022) are protective for the development of the disease, and the TGG haplotype (OR = 2.19 at pperm = 0.001) is associated with an increased risk of developing POAG in women. [ABSTRACT FROM AUTHOR]

Gender-specific features of associations of functionally significant polymorphic loci of matrix metalloproteinase genes with the development of peptic ulcer disease (PUD) in the population of the European part of Russia were studied. The study included 305 men (patients with PUD—188, control group—117) and 441 women (patients with PUD—211, control group—230). Ten functionally significant polymorphic loci of matrix metalloproteinase genes were genotyped: rs1799750 MMP1, rs243865 MMP2, rs679620 MMP3, rs1940475 MMP8, rs3918242, rs3918249, rs17576, rs3787268, rs2250889, rs17577 of the MMP9 gene. Associations of polymorphic loci of MMP genes with PUD were studied by logistic regression (dominant, recessive, and additive genetic models of allele interaction were evaluated). It was found that alleles C rs3918249 (OR = 1.61, pperm = 0.048) and G rs17576 (OR = 1.48–2.08, pperm ≤ 0.042) of the MMP9 gene were risk factors for the occurrence of PUD in men. In women, the 2G rs1799750 allele of the MMP1 gene had a protective value for the development of the disease (OR = 0.74, pperm = 0.047). Polymorphic loci associated with PUD in men and women exhibit pronounced epigenetic effects (they affect the affinity of DNA motifs for various transcription factors, are located in the region of promoters and enhancers in the stomach and duodenum, and are associated with gene expression in various parts of the digestive system). Gender-specific features of associations of polymorphism of MMP genes with the development of PUD were revealed: rs3918249 and rs17576 of the MMP9 gene determine the susceptibility to the development of PUD in men, and rs1799750 of the MMP1 gene determines the susceptibility in women. [ABSTRACT FROM AUTHOR]

We studied the associations of newborn weight with polymorphic loci of growth factor genes in pregnant women with preeclampsia (PE) and considered their regulatory potential. In the group of pregnant women with PE (n = 190), a molecular genetic study of five polymorphic loci of growth factor genes was performed: rs4444903 EGF, rs833061 VEGFA, rs2981582 FGFR2, rs6214 IGF1, rs1800469 TGFβ1. Newborn somatometry was performed using standard methods. Associations of the studied polymorphic loci with newborn weight were studied using log-linear regression analysis. It was found that the genetic risk factor for the birth of small children in pregnant women with PE is the allele C of the rs833061 polymorphism of the VEGFA gene (pperm = 0.002): women with the T/T genotype have the highest newborn weight (on average 3524 g), while women with the C/C genotype have the minimum newborn weight (on average 3415 g). It is shown that the allele C of polymorphic locus rs833061 is associated with low transcription of the VEGFA gene in the thyroid gland and a higher level of alternative splicing of the VEGFA gene transcript in skeletal muscle, increases the affinity of DNA for transcription factors BCL, Pax-5, and Znf143, and affects the interaction of DNA with more than 20 different regulatory proteins (CTCF, RAD21, ZNF263, MAX, etc.). It is revealed that polymorphism rs833061of the VEGF gene in pregnant women with PE is associated with weight of the newborn and has considerable regulatory potential. [ABSTRACT FROM AUTHOR]

Objectives. To study the interaction of polymorphic markers for matrix metalloproteinases (MMP) and chronic stress on formation of stroke on the background of hypertensive disease. Materials and methods. A total of 830 patients were studied: 303 patients with ischemic stroke on the background of hypertensive disease and 527 patients with hypertensive disease without stroke. SNP for metalloproteinases were studied using the real-time polymerase chain reaction. The functional significance and influences of polymorphic loci on gene expression were studied using the HaploReg (v4.1) (http://archive.broadinstitute.org) and GTEx-portal (http://gtexportal.org) services. Results and conclusions. An association was found between the GG rs11568818 genotype of the MMP7 gene and a high risk of developing stroke in patients experiencing regular stress (odds ratio (OR) 1.71). The 5A allele and the 5A/5A genotype of rs3025058 of the MMP3 gene had protective effects on development of stroke in people without histories of chronic stress (OR 0.73 and OR 0.60, respectively). The SNP studied here were located in the histone protein H3K4me1 and H3K4me3 region, which is hypersensitive to DNase 1 and binds regulatory proteins and transcription factors, while the polymorphic rs11568818 locus is linked with the level of expression of the MMP7 gene. [ABSTRACT FROM AUTHOR]

The frequencies and spectra of surnames have been analyzed in groups of raions (districts) of the Belgorod oblast (region) with different degrees of population subdivision. The “family name portraits” of districts with low (0.00003 < < f*r < 0.00022, $$\overline {f_r^ * } $$ = 0.00015) and moderate (0.00023 < f*r < 0.00042, $$\overline {f_r^ * } $$ = 0.00029) inbreeding levels are similar both to each other and to the “family name portrait” of the Belgorod oblast as a whole. Districts with high subdivision levels (0.00043 < f*r < 0.00125, $$\overline {f_r^ * } $$ = 0.00072) had very distinctive surname spectra and the highest surname frequencies. Intense immigration to the Belgorod oblast significantly affects its population genetic structure, decreasing the population subdivision. [ABSTRACT FROM AUTHOR]