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The purpose of this work was to find a link between the breast cancer (BC)-risk effects of sex hormone-binding globulin (SHBG)-associated polymorphisms and obesity. The study was conducted on a sample of 1498 women (358 BC; 1140 controls) who, depending on the presence/absence of obesity, were divided into two groups: obese (119 BC; 253 controls) and non-obese (239 BC; 887 controls). Genotyping of nine SHBG-associated single nucleotide polymorphisms (SNP)—rs17496332 PRMT6, rs780093 GCKR, rs10454142 PPP1R21, rs3779195 BAIAP2L1, rs440837 ZBTB10, rs7910927 JMJD1C, rs4149056 SLCO1B1, rs8023580 NR2F2, and rs12150660 SHBG—was executed, and the BC-risk impact of these loci was analyzed by logistic regression separately in each group of obese/non-obese women. We found that the BC-risk effect correlated by GWAS with the SHBG-level polymorphism rs10454142 PPP1R21 depends on the presence/absence of obesity. The SHBG-lowering allele C rs10454142 PPP1R21 has a risk value for BC in obese women (allelic model: CvsT, OR = 1.52, 95%CI = 1.10–2.11, and pperm = 0.013; additive model: CCvsTCvsTT, OR = 1.71, 95%CI = 1.15–2.62, and pperm = 0.011; dominant model: CC + TCvsTT, OR = 1.95, 95%CI = 1.13–3.37, and pperm = 0.017) and is not associated with the disease in women without obesity. SNP rs10454142 PPP1R21 and 10 proxy SNPs have adipose-specific regulatory effects (epigenetic modifications of promoters/enhancers, DNA interaction with 51 transcription factors, eQTL/sQTL effects on five genes (PPP1R21, RP11-460M2.1, GTF2A1L, STON1-GTF2A1L, and STON1), etc.), can be "likely cancer driver" SNPs, and are involved in cancer-significant pathways. In conclusion, our study detected an obesity-dependent association of the rs10454142 PPP1R21 with BC in women. [ABSTRACT FROM AUTHOR]

We aimed to explore the potential link of maternal age at menarche (mAAM) gene polymorphisms with risk of the fetal growth restriction (FGR). This case (FGR)–control (FGR free) study included 904 women (273 FGR and 631 control) in the third trimester of gestation examined/treated in the Departments of Obstetrics. For single nucleotide polymorphism (SNP) multiplex genotyping, 50 candidate loci of mAAM were chosen. The relationship of mAAM SNPs and FGR was appreciated by regression procedures (logistic/model-based multifactor dimensionality reduction [MB-MDR]) with subsequent in silico assessment of the assumed functionality pithy of FGR-related loci. Three mAAM-appertain loci were FGR-linked to genes such as KISS1 (rs7538038) (effect allele G-odds ratio (OR)allelic = 0.63/pperm = 0.0003; ORadditive = 0.61/pperm = 0.001; ORdominant = 0.56/pperm = 0.001), NKX2-1 (rs999460) (effect allele A-ORallelic = 1.37/pperm = 0.003; ORadditive = 1.45/pperm = 0.002; ORrecessive = 2.41/pperm = 0.0002), GPRC5B (rs12444979) (effect allele T-ORallelic = 1.67/pperm = 0.0003; ORdominant = 1.59/pperm = 0.011; ORadditive = 1.56/pperm = 0.009). The haplotype ACA FSHB gene (rs555621*rs11031010*rs1782507) was FRG-correlated (OR = 0.71/pperm = 0.05). Ten FGR-implicated interworking models were founded for 13 SNPs (pperm ≤ 0.001). The rs999460 NKX2-1 and rs12444979 GPRC5B interplays significantly influenced the FGR risk (these SNPs were present in 50% of models). FGR-related mAAM-appertain 15 polymorphic variants and 350 linked SNPs were functionally momentous in relation to 39 genes participating in the regulation of hormone levels, the ovulation cycle process, male gonad development and vitamin D metabolism. Thus, this study showed, for the first time, that the mAAM-appertain genes determine FGR risk. [ABSTRACT FROM AUTHOR]

In our work, the associations of GWAS (genome-wide associative studies) impact for sex-hormone-binding globulin (SHBG)-level SNPs with the risk of breast cancer (BC) in the cohort of Caucasian women of Russia were assessed. The work was performed on a sample of 1498 women (358 BC patients and 1140 control (non BC) subjects). SHBG correlated in previously GWAS nine polymorphisms such as rs780093 GCKR, rs17496332 PRMT6, rs3779195 BAIAP2L1, rs10454142 PPP1R21, rs7910927 JMJD1C, rs4149056 SLCO1B1, rs440837 ZBTB10, rs12150660 SHBG, and rs8023580 NR2F2 have been genotyped. BC risk effects of allelic and non-allelic SHBG-linked gene SNPs interactions were detected by regression analysis. The risk genetic factor for BC developing is an SHBG-lowering allele variant C rs10454142 PPP1R21 ([additive genetic model] OR = 1.31; 95%CI = 1.08–1.65; pperm = 0.024; power = 85.26%), which determines 0.32% of the cancer variance. Eight of the nine studied SHBG-related SNPs have been involved in cancer susceptibility as part of nine different non-allelic gene interaction models, the greatest contribution to which is made by rs10454142 PPP1R21 (included in all nine models, 100%) and four more SNPs—rs7910927 JMJD1C (five models, 55.56%), rs17496332 PRMT6 (four models, 44.44%), rs780093 GCKR (four models, 44.44%), and rs440837 ZBTB10 (four models, 44.44%). For SHBG-related loci, pronounced functionality in the organism (including breast, liver, fibroblasts, etc.) was predicted in silico, having a direct relationship through many pathways with cancer pathophysiology. In conclusion, our results demonstrated the involvement of SHBG-correlated genes polymorphisms in BC risk in Caucasian women in Russia. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to investigate the role of functionally significant polymorphisms of the MMP1, MMP3, and MMP9 genes in the development of exfoliation glaucoma (XFG) in the Caucasian population of Central Russia. Methods: The study sample consisted of 724 participants, including 328 patients with XFG and 396 individuals in the control group. The participants were of Russian ethnicity (self-reported) born in Central Russia. The participants were genotyped at 8 functionally significant polymorphisms of the MMP genes (rs3918242, rs3918249, rs17576, rs3787268, rs2250889, rs17577 MMP9, rs679620 MMP3, and rs1799750 MMP1). The association analysis was performed using logistic regression. Two polymorphisms, which were associated with XFG, and 12 polymorphisms linked to them (r2 ≥ 0.8) were analyzed for their functional significance in silico. Results: Allele C of rs3918249 MMP9 was associated with XFG according to the additive model (OR = 0.75, 95% CI: 0.56–0.93, pperm = 0.015), and allele G of the rs2250889 MMP9 locus was associated with XFG according to the additive (OR = 1.59, 95% CI: 1.10–2.29, pperm = 0.013) and dominant (OR = 1.68, 95% CI: 1.11–2.56, pperm = 0.016) models. Two XFG-associated loci of the MMP9 gene and 12 SNPs linked to them had a significant regulatory potential (they are located in the evolutionarily conserved regions, promoter and enhancer histone marks, the DNAase-hypersensitivity regions, a region binding to regulatory protein, and a region of regulatory motifs) and may influence the expression of 13 genes and alternative splicing of 4 genes in various tissues and organs related to the pathogenesis of XFG. Conclusion: Allele C rs3918249 MMP9 decreased risk for XFG (OR = 0.75), and allele G of the rs2250889 MMP9 locus increased risk for XFG (OR = 1.59–1.68) in the Caucasian population of Central Russia. [ABSTRACT FROM AUTHOR]

To study the associations of polymorphisms of the NDRG1 gene, which is differentially expressed in the placenta, with the risk of preeclampsia (PE) development. The study group included 997 women: 366 pregnant women with preeclampsia and 631 women with physiological pregnancy. Clinical and laboratory examination of pregnant women was carried out in the Perinatal Center of the Belgorod Regional Clinical Hospital of St. Joasaph. DNA was isolated from peripheral venous blood lymphocytes by phenol-chloroform extraction. All women underwent typing of four single nucleotide polymorphisms of the N-myc downstream regulated gene 1 (NDRG1). The analysis of SNPs associations with the development of preeclampsia was performed using logistic regression analysis within the framework of additive, dominant and recessive genetic models. The average age in the group with preeclampsia was 0.75 years higher compared to the control group (p = 0.01). Among pregnant women with PE, body weight and body mass index exceeded those of the control group (p = 0.0001). Also, in this group, the percentage of women with obesity is 2.26 times higher (p = 0.001). The analysis of risk factors for PE revealed a higher incidence of arterial hypertension before pregnancy and a history of preeclampsia in the patient group as compared with the control (p = 0.0001). Compared with the control group, women with PE have a greater number of pregnancies (1.32 times, p = 0.03) due to a greater number of stillbirths (p = 0.02), miscarriages (0.01), and artifactual abortions (p = 0.0005). The rs12678229 NDRG1 allele A was found to be associated with the development of preeclampsia in the framework of the recessive model (OR = 1.46, 95% Cl 1.01- 2.12, p = 0.046). The associations of other studied polymorphic markers with the development of preeclampsia were statistically insignificant. Thus, the rs12678229 NDRG1 allele is a risk factor for the development of preeclampsia among the women of the Central Black Earth Region of Russia. [ABSTRACT FROM AUTHOR]

Objectives: The objectives were to study the role of maternal and fetal risk factors in the development of placental insufficiency (PI) and fetal growth retardation syndrome (FGRS). Materials and Methods: The case-control study sample included 497 females in the third trimester of pregnancy recruited during 2009-2013. All the patients were divided into two groups, with the development of fetal growth retardation (n = 250) and without it (n = 247), respectively. Results: The prevalence of spontaneous abortions is higher (18.40%) in the group of pregnant women with FGRS compared with the control group (10.12%, χ2 = 6.29, P = 0.01), due to abortions in the first trimester (14.40% and 8.10%, respectively, χ2 = 4.33, P = 0.04). The parents of women with FGRS (21.60%) had an anamnesis aggravated by venous thrombosis or stroke/heart attack, which is higher compared to 10.12% of cases among pregnant women without FGRS (10.12%, χ2 = 11.40, P = 0.002). Spontaneous venous thrombosis occurred in 15.2% of all cases among parents of patients with FGRS compared to 8.10% among parents of patients without FGRS (χ2 = 5.41, P = 0.02). 8.40% of mothers of patients with FGRS had a burdened obstetric history, which is higher than in control patients (3.24%, χ2 = 5.12, P = 0.02). Conclusions: Thus, as a result of the study, risk factors for the development of PI in FGRS are established. These include a burdened thrombotic history in relatives, a burdened obstetric history in the patient's mother, and a history of spontaneous abortions. [ABSTRACT FROM AUTHOR]

Objectives: The objective of this study is to compare clinical and laboratory indicators in pregnant women with preeclampsia (PE) compared with women with physiological pregnancy. Materials and Methods: The study group included 459 women: 209 women with physiological pregnancy and 250 pregnant women with PE. We studied coagulogram data, biochemical blood analysis, and the level of systolic and diastolic blood pressure before and during pregnancy. Results: It was established that pregnant women with PE have higher blood pressure indicators than women without PE. The content of fibrinogen in the blood and the rate of thrombin time in pregnant women with PE are higher, and the prothrombin ratio, partial thromboplastin time, and the total protein content in the blood are lower compared to women without PE (P < 0.01). Conclusions: Thus, as a result of this study, significant associations of blood pressure and hemostasis in pregnant women with PE were established, compared with women with physiological pregnancy. [ABSTRACT FROM AUTHOR]

Data on the allele and genotype frequencies of the five single nucleotide polymorphisms (SNPs) 5 genes - rs1514175 TNNI3K , rs713586 RBJ, rs887912 FANCL , rs2241423 MAP2K5 , rs12444979 GPRC5B in Russian women are presented. Several genome-wide association studies identified these SNPs could be significant genetic markers associated with body mass index (BMI). Standard methods were used for collecting of the anthropometric characteristics (height and weight). We calculated the frequencies of alleles and genotypes of five SNPs in 5 groups: all samples, underweight (BMI<18.50), normal weight (18.50-24.99), overweight (25.00-29.99), obese (>30.00)., (© 2019 The Authors.)

Aim: To examine the association of genetic polymorphisms (-308)G/A TNFα , (+250)A/G Ltα , (+36)A/G TNFR1 , (+1663)A/G TNFR 2 with the development of primary open angle glaucoma (POAG) among people in Central Russia., Methods: The study sample included 443 individuals, of which 252 patients with POAG and 191 individuals in the control group. Genotyping of (-308)G/A TNFα , (+250)A/G Ltα , (+36)A/G TNFR1 , (+1663)A/G TNFR 2 was performed using polymerase chain reaction. The distribution of alleles and genotypes of the studied DNA markers in the groups was examined by 2×2 contingency tables and χ 2 with the Yates's correction for continuity and odds ratios (OR) with 95% confidence intervals (CI)., Results: Allele (-308)G TNFα ( Р =0.01, OR=1.78, 95%CI 1.12-2.85) was identified as a risk factor for POAG. Homozygotes (-308) AA TNFα are at a lowest risk for development of the disease ( Р =0.01, OR=0.0005). The following combination of genetic variants of cytokines were associated with a reduced risk of POAG: (+1663)A TNFR2 and (+250)G Ltα (OR=0.34)., Conclusion: Genetic polymorphisms (-308)G/A TNFα , (+250)A/G Ltα , (+1663)A/G TNFR2 associated with the development of POAG in the population of Central Russia.

Introduction: Malfunctioning of the cardiovascular system during pregnancy may be responsible for adverse effects on the 'mother-fetus' system. The cardiovascular system of a pregnant woman develops adaptation to the increased load. Angiotensin-converting enzyme (ACE) is known to play an important role in the adaptation. The present study was designed to investigate whether the insertion-deletion (I/D) polymorphism of the ACE gene is associated with the level of arterial blood pressure in women before and during pregnancy., Materials and Methods: The level of blood pressure was measured in 591 Russian women (Central Russia) before and during (37-40 weeks term) pregnancy. The women were divided into three groups which were hypertensive, hypotensive, and normotensive according to blood pressure level. Genotyping of the ACE I/D polymorphism was performed using polymerase chain reaction (PCR) and amplified fragment length polymorphism assay., Results: Women with genotype DD showed the highest blood pressure level both during and at the end of pregnancy (p<0.05). The highest frequencies of allele D and genotype DD were found in pregnant women in the hypertensive group., Conclusions: The deletion variant of the ACE gene is associated with high blood pressure level at the end of pregnancy., (© The Author(s) 2013.)