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The aim of this review is to summarize current understandings of the genetic risk factors for the development of breast cancer (BC), evaluate the role of germline mutations and single nucleotide polymorphisms associated with the disease, based on genome-wide association studies (GWAS) and other associative studies. The search for relevant sources was conducted in PubMed, Medline, Cochrane Library, eLIBRARY, and the NHGRI-EBI Catalog of GWAS. The analysis includes works published from January 2007 to December 2022. A total of 197 sources focused on the role of genetic factors in the development of BC were found. Search queries included data on associations of various molecular-genetic markers – germline mutations, and single nucleotide polymorphisms – with the formation of BC. From this body of work, 45 studies were included in the current review. The inclusion criterion for the analysis wasthe presence of GWAS data and associative studies conducted among patients with representative samples with the necessary power. Additionally, results characterizing the clinical-pathological significance (association with molecular subtypes of BC, therapy features, disease prognosis) of BC genetic factors were evaluated. Excluded from the analysis were data from associative studies of candidate genes for malignant breast neoplasms that are morphologically not carcinomas, performed on small (non-representative) patient samples and control groups. Mutations in genes with high and moderate penetrance (BRCA1/2, CHEK2, PALB2, etc.) are associated with the onset of BC in 5 % of cases. Among families with two or more members affected by BC, their share reaches only 30–40 %. GWAS data revealed the role of more than 180 polymorphic loci associated with BC, which determine a heritability rate of about 18 %. According to twin studies, this rate is 1.7 times higher, reaching 31 %. Meanwhile, the contribution of environmental factors is no more than 16 %. The proportion of unidentified hereditary factors in BC formation is about 8 %. However, contemporary studies of associations of various candidate genes (ESR1/2, IGF1, EGFR, VEGF, TNFα, MMPs, etc.), whose signaling pathways regulate BC tumor progression, show their involvement in carcinogenesis. Thus, the unknown heritability in BC formation may reach 40 %. The proportion of germline mutations in major BC predisposition genes in the population is low. Genetic variations within the same gene (e.g., BRCA1) show ethnic or territorial diversity. Nevertheless, a significant portion of BC heritability is determined by various candidate genes, whose role in forming individual BC risk is demonstrated by GWAS. Substantial evidence on the involvement of key carcinogenesis-regulating genes in BC development is being accumulated. Each of the three considered groups of genetic factors has important clinical-pathological significance and can influence the course and prognosis of the disease.

Aim: to evaluate a role of polymorphic variants rs4149056 SLCO1B1, rs8023580 NR2R2 and rs7910927 JMJD1C in developing obesity-related female breast cancer (BC).Materials and Methods. A retrospective comparative study was performed on a sample of 1,498 women (358 BC patients and 1,140 control subjects) stratified into 2 groups based on verified obesity: obese (119 BC patients and 253 control subjects) and non-obese (239 BC patients and 887 control subjects). Genotyping of three single nucleotide polymorphisms (SNP) – rs7910927 JMJD1C, rs8023580 NR2F2, rs4149056 SLCO1B1 was performed to be further analyzed separately in each group of obese and non-obese women for associations of such loci and interplay with breast cancer.Results. Polymorphisms rs8023580 NR2F2, rs4149056 SLCO1B1 and rs7910927 JMJD1C are not independently associated with BC in obese and non-obese women, whereas their interlocus interactions are BC-significant in each of the examined groups (pperm = 0.047 and pperm = 0.0012, respectively). Among obese women, the combination of TC-TT-GG genotypes (for rs8023580–rs4149056–rs7910927) is associated with a low risk of developing BC (β = –2.45), whereas the combination of TC-TC-GG genotypes is associated with increased BC risk (β=1.42). In non-obese women, a combination of the TC-TT-GT genotypes (β = –0.47) has a protective effect on the BC occurrence, and the risk effect is coupled to TC-TC-GT (β = 0.91) and TC-CC-GT (β = 1.45). The appearance of allele C rs4149056 in female genotype and its increased "concentration" results in higher BC risk.Conclusion. The allele variant C rs4149056 in the interlocus interactions between the SLCO1B1, NR2F2 and JMJD1C genes is a "universal" factor that elevates BC risk in both obese and non-obese women. The genotype GG rs7910927 is BC-significant in interlocus interactions in obese women, whereas in non-obese women it is coupled to the genotype GT rs7910927.

Aim: to assess associations between folate cycle gene polymorphism and neonatal birth weight in pregnant women with fetal growth retardation (FGR) and related functional effects in population of the Central Black Earth Region.Materials and Methods. 98 cases of women with FGR were enrolled to a retrospective molecular and genetic screening to assess prevalence 5 SNPs (single nucleotide polymorphisms) in genes involved in folic acid cycle and methionine metabolism (rs699517 TYMS, rs2790 TYMS, rs1979277 SHMT1, rs1805087 MTR, rs1801394 MTRR).Results. It was found out that allele A of the rs1801394 MTRR was associated with a lower neonatal birth weight (recessive model: β = –0.34 ± 0.13; p = 0.009). This polymorphic locus exerts crucial functional effects by determining the amino acid substitution in methionine synthase reductase (Ile22Met) localized in the region of modified histones, which mark enhancers and promoters in ectoderm, endoderm and mesoderm cell cultures, primary osteoblast cells, brain, fat nuclei, skeletal muscles, etc. In addition, rs1801394 MTRR is found DNA sites (motifs) responsible for sensitivity to transcription factors STAT and TBX5 being also related to MTRR gene mRNA expression level in subcutaneous and visceral adipose tissue, thyroid gland, fibroblast cell culture as well as various brain regions.Conclusion. Thus, the allele A of the rs1801394 polymorphism in MTRR gene is a risk factor for a lower neonatal birth weight.

Aim: to identify specific associations between genes polymorphism associated with sex hormone-binding globulin (SHBG) level and breast cancer (BC) of various molecular biological subtypes.Materials and Methods. The retrospective comparative study was conducted using specimens collected from 261 patients with BC of two molecular biological subtypes – luminal A/B (n = 153) and triple negative (n = 108) as well as 1140 women in control group. All study participants (n = 1401) underwent a molecular genetic study of four single nucleotide polymorphism (SNP) loci, which showed a relationship with circulating SHBG level in previously conducted genome-wide association study (GWAS): rs12150660 SHBG, rs10454142 PPP1R21, rs780093 GCKR, rs17496332 PRMT6.Results. The analysis revealed an association between SHBG SNP candidate genes and a BC risk in patients with luminal A/B subtypes and lacked significant associations between the loci assessed and triple negative BC subtype. CC female genotype of rs10454142 PPP1R21 increased a risk of luminal A/B subtypes BC by more than 2-fold (recessive model [CC vs. TC+TT]; odds ratio = 2.07; 95 % confidence interval = 1.14–3.77; p = 0.017; pperm = 0.018). This SNP is localized in functionally "significant" regions of the genome (enhancers/active enhancers, promoters/active promoters) and affects methylation level in several hepatocyte DNA sites [cg15846641 (chr2:48541264)].Conclusion. The genetic variant rs10454142 PPP1R21 is associated with the risk of developing ВС luminal A/B subtypes, but not with ВС triple negative subtype.

The article presents current data on the etiopathogenesis and risk factors of breast cancer (BC). The search for the sources was carried out in the PubMed, Medline, Cochrane Library, eLIBRARY, NHGRI-EBI Catalog of GWAS systems, publications from January 2000 to December 2022 were included. The interaction of definite risk factors, endocrine stimuli and genetic disorders causes activation / inactivation of various signaling pathways that directly or indirectly affect carcinogenesis. According to modern genetic evaluations, the contribution of the hereditary component to the formation of BC reaches 40 %. Interactiones between various risk factors form several molecular subtypes of breast carcinomas, differing in receptor status and clinical course, as well as therapeutic approaches. The details of the interaction of etiopathogenetic factors of BC are not clear, and often have a multidirectional character. Matrix metalloproteinases (MMPs) regulate the mechanisms of proliferation and apoptosis, invasion and metastasis, formation of the tumor microenvironment, neoangiogenesis, as well as intergenic signaling interactions, being an important link in the pathogenesis of BC.

Here, we analyze the data on genetic factors involved in developing endometriosis available in current publications. To date, the genome-wide associative studies (GWAS) have revealed more than 190 loci associated with endometriosis development, however, only few polymorphisms were associated with this disease identified in two GWAS (rs1537377 CDKN2B-AS1, rs71575922 SYNE1, rs11674184 GREB1, rs1903068 KDR, rs2235529 WNT4, rs7412010 CDC42), and only one rs12700667 TSEN15P3/MIR148A polymorphic locus in four studies. Several polymorphisms located in the region of two genes GREB1 (rs11674184, rs13394619, rs35417544) and WNT4 (rs2235529, rs12037376, rs7521902) are associated with endometriosis in several GWAS. The association of 5 polymorphic loci with endometriosis was confirmed in two or more replication studies: rs13394619 GREB1, rs7521902 MIR4418/WNT4, rs1250248 FN1 and rs6542095 CKAP2L/IL1A – in two studies, rs12700667 TSEN15P3/MIR148A – in four studies. At the same time, the relationship between the vast majority of GWAS-significant polymorphic loci (more than 95 %) and endometriosis has not been confirmed in other independent studies, necessitating a need to continue endometriosis-related genetic studies, including those aimed at confirming previously identified associations.

Aim: to investigate an association between polymorphism in the MMP2, MMP8, MMP9 genes and severe breast cancer (BC).Materials and Methods. Retrospective comparative study was conducted by assessing a cohort of 345 BC patients: 254 patients at stage I–II and 91 at stage III–IV. Genotyping of the three single nucleotide polymorphisms in the MMP2 (C>T rs243865), MMP8 C>T rs1940475), and ММР9 (C>T rs3918242) genes was performed. A comparative analysis of the genetic characteristics of patients with stage I–II and stage III–IV of the disease was performed.Results. The allele variant T rs1940475 (C>T) of the MMP8 gene in BC patients at stage I–II (0.512) was found by 1.2-fold more often compared with patients at stage III–IV of the disease (0.428; pperm = 0.05). According to allelic (odds ratio (OR) = 0.71; 95 % confidence interval (CI) = 0.51–1.00; pperm = 0.05) and additive (OR = 0.69; 95 % CI = 0.48–0.99; pperm = 0.05) genetic models, the allele T rs1940475 (C>T) of the MMP8 gene has protective effect for developing stage III–IV BC. The polymorphic locus rs1940475 (C>T) determines the amino acid substitution in the MMP8 protein (p.K87E) and DNA binding to the transcription factors NF-AT1, MYC and CIZ, is associated with the expression of the genes MMP27 and RP11-817J15.3 acting as an enhancer regulatory site in primary breast epithelial cells. Single nucleotide polymorphism in the MMP2 (C>T rs243865), ММР9 (C>T rs3918242) genes is not associated with severe BC (stages III–IV).Conclusion. The single nucleotide polymorphism rs1940475 in the MMP8 gene is a protective factor protecting against severe BC course.

Aim: to evaluate a relationship between newborn weight and single-nucleotide polymorphisms rs5918 ITGB3, rs1126643 ITGA2, rs5985 F13A1 in pregnant women with preeclampsia (PE) and fetal growth retardation (FGR).Materials and Мethods. In this prospective comparative study, molecular genetic testing for the three polymorphic loci of hereditary thrombophilia candidate genes – rs1126643 ITGA2, rs5918 ITGB3, and rs5985 F13A1 was performed in 70 pregnant women with PE and FGR. Newborn somatometry was performed using standard methods. To assess functional effects of the rs5985 polymorphism of the F13A1 gene associated with newborn weight, we applied online bioinformatic programs GTEx Portal and HaploReg (assessing a relationship between polymorphism and level of gene transcription and related epigenetic effects).Results. The rs5985 polymorphism of the maternal F13A1 gene is associated with newborn weight according to allelic (â = 156.60; pperm = 0.05) and additive (â = 155.20; pperm = 0.05) genetic models. The polymorphic locus rs5985 of the F13A1 gene is characterized by pronounced pleiotropic regulatory effects in vivo: it determines the amino acid substitution in the A1 subunit of coagulation factor XIII (Val35Leu), associated with the activity of blood clotting factor XIII, localized in the DNase 1 hypersensitivity region, determines DNA affinity to 11 transcription factors (AP-2, CACD, EBF, ERalpha-a, ESR2, Hic1, Klf4, Klf7, SP1, ESR1 and TFAP2C), located in the region of modified histones, marking enhancers and promoters in the culture of ectoderm, endoderm and mesoderm cells, placenta, fetal brain and adrenal glands, progenitor cells and myoblasts in skeletal muscle, adipocytes, brain etc.Conclusion. The rs5985 polymorphism of the F13A1 gene in pregnant women with PE and FGR is associated with newborn weight.

Aim: to study a relation between a single-nucleotide polymorphism in the estrogen receptor beta (ESR2) gene and age of menarche in women of the Central Black Earth region of Russia.Materials and Мethods. There were enrolled 696 women to the retrospective study. All subjects were interrogated data regarding the age of menarche. Three polymorphic loci rs4986938, rs1256031, and rs10144225 of the ESR2 gene were genotyped by using the TaqMan probe polymerase chain reaction. The functional epigenetic effects of the rs4986938 ESR2 menarche-associated polymorphism were studied by using the online HaploReg software.Results. There were found out associations of ESR2 rs4986938 polymorphism with the age of menarche in Russian women of the Central Black Earth region of the Russian Federation. Women with the rs4986938 ESR2 polymorphism allele A in the genotype (genotypes A/A and G/A) had menarche at the age of 12.71 ± 1.03 years, which is 0.20 years later than in women lacking it in the genotype (genotype G/G), who had menarche at age of 12.51 ± 1.05 years (pperm = 0,01). The rs4986938 ESR2 polymorphism is characterized by pronounced epigenetic effects: it affects affinity for five transcription factors – CTCF, Nr2f2, Pax-6, Pax-8, and RAR, being associated with enhancer and promoter sites in various menarche-significant body tissues and organs, and associated with the expression of the ESR2 geneepigenetic effects: it affects affinity for five transcription factors – CTCF, Nr2f2, Pax-6, Pax-8, and RAR, being associated with enhancer and promoter sites in various menarche-significant body tissues and organs, and associated with the expression of the ESR2 gene.Conclusion. The rs4986938 polymorphic locus of the ESR2 gene is associated with age of menarche in women in the European part of Russia.

Aim: to analyze the association of the ESR1 gene polymorphic loci rs2234693, rs9340799, and rs3798577 with developing preeclampsia (PE) with fetal growth retardation (FGR). Materials and Methods. The study was performed while analyzing a sample of 400 women: 76 pregnant women with PE and FGR and 324 with a physiological course of pregnancy. Three polymorphic loci of the ESR1 gene (rs2234693, rs9340799, and rs3798577) were genotyped. Functional effects of polymorphic loci were evaluated by using the online programs HaploReg (epigenetic effects) and GTEx Portal (relation to gene expression). Results. The development of PE and FGR is associated with the G allele and GG genotype rs9340799 of the ESR1 gene (OR = 1.38; pperm = 0.04 and OR = 2.00; pperm = 0.04, respectively), the T allele rs3798577 of the ESR1 gene (OR = 1.46; pperm = 0.01), and the TG haplotype of the polymorphic loci rs2234693–rs9340799 of the ESR1 gene (OR = 2.08; pperm = 0.009). Polymorphic locirs2234693, rs9340799 ESR1 gene and rs3798577 have an important functional significance in human body being located in the evolutionarily conserved DNA region, affect affinity of regulatory DNA motifs to the eight transcription factors as well as ESR1 gene expression in the thyroid gland, which are positioned in the promoter and enhancer region, DNAse 1 hypersensitivity motif within diverse organs and tissues, and display an important pathogenetic effect for development of PE and FGR. Conclusion. Polymorphic loci rs2234693, rs9340799 and rs3798577 of the ESR1 gene are associated with developing PE and FGR.

Aim. To assess the neuronal damage severity and cognitive status in conditions of unilateral antegrade cerebral perfusion through the brachiocephalic trunk during surgical reconstruction of the thoracic aorta.Material and methods. The study included 144 patients with aneurysm and dissection of the thoracic aorta. Patients underwent reconstructive surgery under cardiopulmonary bypass, unilateral antegrade cerebral perfusion and circulatory arrest. Before and after the intervention, a cognitive status analysis was performed using the Montreal Cognitive Assessment (MoCA), Amatinu test and Schulte tables. The dynamics of neuron-specific enolase (NSE), a marker of neuronal damage, was determined perioperatively.Results. The duration of cardiopulmonary bypass was 155 [115; 201] min, cardioplegic arrest — 100 [72; 150] min, unilateral perfusion — 20 [15; 51] min,circulatory arrest — 20 [15; 30]min.Hospital mortality was 7% (10 cases). Neurological complications were noted in 12 (8%) cases. All patients in the postoperative period (within 24 hours) showed an increase in NSE compared with baseline values (3,3 μg/L and 2,07 μg/L, respectively, p=0,0003), but not exceeding the upper limit of normal (9,9 μg/l). According to the results of psychometric tests, which were carried out upon admission to the hospital and 2 weeks after the operation, there were no negative changes (MoCA test: 24 [21; 26] points — 26 [24; 27] points, p=0,00001; Schulte tables: 288 [240; 368] s — 278 [241; 328] s, p=0,01; Amatuni sample 264 [216; 297] s — 254 [221; 280] s, p=0,57).Conclusion. Based on the analysis of the perioperative dynamics of neuronspecific enolase and cognitive tests, unilateral cerebral perfusion through the brachiocephalic trunk is effective and relatively safe. This method of perfusion protection of the brain helps to minimize postoperative neurological complications during operations on the thoracic aorta.

Aim. To compare the effectiveness and safety of ascending aortic hemiarch replacement performed during hypothermic circulatory arrest with different temperature regimens.Material and methods. The study included 104 patients with ascending aortic aneurysm, who underwent ascending aortic hemiarch replacement under hypothermic circulatory arrest and antegrade cerebral perfusion. Depending on the temperature regimen, all patients were divided into two comparable groups: group 1 (n=28) — patients operated on under mild hypothermia (29-31oС), group 2 (n=76) — patients operated on under moderate hypothermia (25-28oC).Results. Comparative analysis of intraoperative data between groups of patients with mild and moderate hypothermia revealed a significant difference in the duration of cardiopulmonary bypass (111 [97; 135] min vs 125 [108.5; 170] min, p=0,031) and surgery (240 [210; 270 ] min vs 275 [240; 330] min, p=0,003). In the early postoperative period, the best results were also obtained in patients of mild hypothermia group. In these patients, compared with moderate hypothermia group, there was a lower frequency of reoperation due to bleeding (3,5% vs 5,2%, p=0,572), a decrease in transfused fresh frozen plasma volume (2 [2; 4] vs 4 [2; 4], p=0,03), a decrease in the ventilatory support duration (10 [7; 16] hours vs 18 [10; 24] hours, p=0,002), as well as a bed-day decrease in intensive care unit (2 [2; 3] and 3 [2; 4] days, p=0,005). No neurologic deficit was found in any of the patients. In-hospital mortality had no significant intergroup differences (p=0,541).Conclusion. An increase in the temperature regimen during the ascending aortic hemiarch replacement performed under hypothermic circulatory arrest is relatively safe in relation to early postoperative complications. Mild hypothermia does not increase early postoperative surgical risks compared to moderate hypothermia.

Aim: to analyze the association of polymorphic loci rs2234693, rs9340799, and rs3798577 of the ESR1 gene with the development of preeclampsia (PE) with fetal growth retardation (FGR) and to consider their regulatory potential.Materials and Methods. The present study was performed on a sample of 400 women: 76 pregnant women with PE and FGR and 324 with a physiological course of pregnancy. Three polymorphic loci of the ESR1 gene (rs2234693, rs9340799, and rs3798577) were genotyped. Functional effects of polymorphic loci were evaluated using the online programs HaploReg (epigenetic effects) and GTExportal (relation to gene expression).Results. The development of PE and FGR is associated with the G allele and GG genotype rs9340799 of the ESR1 gene (OR = 1.38; pperm = 0.04 and OR = 2.00, pperm = 0.04 respectively), the T allele rs3798577 of the ESR1 gene (OR = 1.46; pperm = 0.01), and the TG haplotype of the polymorphic loci rs2234693–rs9340799 of the ESR1 gene (OR = 2.08; pperm = 0.009). Polymorphic loci rs2234693, rs9340799 ESR1 gene and rs3798577 have important functional significance in the organism are evolutionary conservative region of DNA, affect affinnity regulatory DNA motifs by 8 transcription factors and gene expression ESR1 in the thyroid gland, located in the region of promoters and enhancers, the region of hypersensitivity to DNase 1 in various organs and tissues, has important pathogenetic importance for the development of PE and FGR.Conclusion. Polymorphic loci rs2234693, rs9340799 and rs3798577 of the ESR1 gene are associated with the development of PE and FGR.

In modern medical practice, contrast-induced nephropathy (CIN) is an urgent problem in patients with acute coronary syndrome that underwent percutaneous interventions. It worsens prognosis, increases the number of cardiovascular complications and the length of hospital stay. Despite the use of modern radiocontrast agents, the incidence of CIN can increase in a certain patients up to 50%. Risk factors for CIN can be associated both with the patient and directly with the x-ray procedures. The diagnosis is mainly based on the pre- and postprocedural determination of creatinine. However, more modern biomarkers of kidney injury can be used at present, which allow diagnosing the acute kidney injury as soon as possible. A huge role is played not only by treatment, but also by the prevention of CIN, which consists in the timely identification of high-risk patients. The current study presents the main points of pathogenesis, methods for diagnosing CIN, as well as methods for its prevention and treatment in patients with acute coronary syndrome.

Aim. To study the clinical features and risk factors (RF) associated with the development of acute coronary syndrome (ACS) in young patients.Material and methods. The study included 474 patients with ACS. Depending on age, patients were divided into 2 groups. The first group consisted of 299 patients of young age (25-44 years), the comparison group consisted of 175 patients of mean and old age (45-74 years). Clinical and anamnestic data, parameters of general clinical and biochemical tests, electrocardiography, echocardiography and coronary angiography were determined in all patients, and polymorphisms in FII G20210-A, FV G1691-A, MTHFR C677-T genes were determined in 116 patients. The control group consisted of 53 healthy volunteers.Results. ACS in patients

Aim. To assess the efficiency of guideline for the prevention of hemorrhagic complications in the early postoperative period.Material and methods. In the period from 2008 to 2017, 166 patients with pathology of the thoracic aorta were operated. The patients were divided into 2 comparable groups: group 1 — patients with reconstructed aortic arch of the type “Hemiarch” (group “hemiarch”, n=90), group 2 — patients with fully reconstructed aortic arch (group “arch”, n=76). All operations were performed with artificial blood circulation, circulatory arrest with moderate hypothermia (25­28° C) and unilateral antegrade cerebral perfusion through the brachiocephalic trunk.Results. The reconstructions of the thoracic aorta in patients of the “hemiarch” group were accompanied by significantly less period of artificial blood circulation (p=0,027), cardiac arrest period (p=0,012), duration of circulatory arrest (p=0,019), and duration of antegrade brain perfusion (p=0,021). The volume of discharge through the drainage was 350 [192;506] ml and 400 [250;723] ml in the “hemiarch” and “arch” groups, respectively (p=0,29). Patients of the “arch” group more often required transfusion of packed red cells (p=0,003), fresh frozen plasma (p=0,0006), platelet concentrate (p=0,002) in comparison with patients of the “hemiarch” group. At the same time, the frequency of bleeding requiring reoperation was comparable in both groups (5,6% versus 5,3%, p=0,969). The 30­day mortality also had no statistically significant differences in patients of the “hemiarch” and “arch” groups (3,3% versus 9,2%, p=0,119).Conclusion. The frequency of hemorrhagic complications requiring reoperation in patients with a fully or partially reconstructed aortic arch does not have significant differences when using the guideline for preventing of hemorrhagic complications, which makes it possible to provide acceptable frequency of bleeding episodes and reoperations in the early postoperative period.

Aim. To study the involvement of polymorphic loci rs1799750 MMR1, rs3025058 MMR3, rs 11568818 MMR7, rs1320632 MMR8 and rs11225395 MMR8 in the development of arterial hypertension (AH) in women of the Central Chernozemny Region of Russia.Material and methods. During the study 584 women were examined: 375 patients with AH and 209 control subjects. Analysis of metalloproteinases’ polymorphic loci was performed using real-time PCR (TagMan probes). Statistical processing of the results was performed using the STATISTICA for Windows 10.0. The regulatory potential of polymorphic loci was analyzed using the HaploReg software (v4.1). Assessment of the effects of single nucleotide polymorphisms on gene expression (cis-eQTL) was performed according to the Genotype-Tissue Expression (GTEx) project.Results. We established that the polymorphic allele G (OR=1,49, 95% CI=1,16-1,92, p=0,002) and the GG genotype (OR=1,64, 95% CI=1,12-2,40, p=0,010) in the rs11568818 locus of MMP7 gene is associated with a high risk of AH in women. Polymorphic marker rs11568818 MMP7 has significant epigenetic effects: located in the region of histones, labeling promoters and enhancers, in the region of binding sites with transcription factors Foxa known1, PLZF, Pou5f1 known2 and GR known4, in binding niche of regulatory proteins TBP, c-FOS, c-Jun. It was found that the polymorphic variant G rs1 1568818 of MMP7 is associated with a reduced level of expression of the MMP7 gene.Conclusion. The polymorphic locus rs11568818 of the MMP7 gene is involved in the development of AH in women of the Central Chernozemny Region of Russia.

В исследование включены больные ишемической болезнью сердца (ИБС) с умеренным (37 чел.) и выраженным (18 человек) гемолизом после коронарного шунтирования в условиях искусственного кровообращения (ИК). До и после операции изучали концентрацию свободного гемоглобина в плазме крови, механическую резистентность эритроцитов, содержание ТБК-активных продуктов и общую антиокислительную активность в эритроцитах, учитывали длительность ИК и объемную скорость перфузии. Установлено, что у больных с выраженным постперфузионным гемолизом уровень ТБК-активных продуктов в эритроцитах после операции нарастает при снижении их общей антиокислительной активности. Развитие умеренного гемолиза не сопровождается изменениями оксидантно-антиоксидантного баланса эритроцитов. Между группами больных отсутствуют достоверные различия в продолжительности ИК, объемной скорости перфузии, механической резистентности эритроцитов на обоих этапах исследования. Таким образом, в основе индивидуально обусловленного выраженного постперфузионного гемолиза лежит свободнорадикальный механизм повреждения эритроцитов, а не механическая травма клеток крови в процессе ИК.

Aim. To investigate whether the functionally relevant -844G>A promotor polymorphism in the catalase (CAT) gene is associated with the development of essential hypertension (EH). Subjects and methods. The investigation enrolled 2,339 unrelated ethnic Russian people, including 1,269 EH patients and 770 apparently healthy individuals. Genotyping of CAT -844G>A (rs769214) polymorphism was performed using a TaqMan real-time polymerase chain reaction assay. Results. The -844A allele (odds ratio (OR)=1.31; 95% confidence interval (CI), 1.04 to 1.64; р=0.02) and the -844AA genotype (OR=1.41; 95% CI, 1.02 to 1.94; р=0.03) were found to be related to a higher risk of EH in the smokers. No association was found between this polymorphism and EH risk in the non-smokers. Conclusion. Smoking is a predisposing factor for development of EH in CAT -844AA genotype carriers.