Maternal polymorphic loci of rs1979277 serine hydroxymethyl transferase and rs1805087 5-methylenetetrahydrofolate are correlated with the development of fetal growth restriction: A case-control study

Background: Key reactions in folate-mediated single-carbon metabolism are regulated by folate cycle enzymes. Violations of the folate cycle may be associated with the occurrence of fetal growth restriction (FGR) in pregnant women. Objective: To study the relationship between polymorphisms of folate cycle genes in the mother with the development of FGR. Materials and Methods: In this case-control study, 122 pregnant women with FGR and 243 pregnant women with normal newborn weight were enrolled. The polymorphic loci of folate cycle genes including rs1805087 5-methylenetetrahydrofolate (MTR) and rs1979277 serine hydroxymethyl transferase (SHMT1) were examined. The study of polymorphisms was carried out through the TaqMan probe detection method using polymerase chain reaction. Logistic regression was used to analyze the associations of the polymorphisms. Results: It was established that the T allele rs1979277 of the SHMT1 gene was correlated with the development of FGR within the framework of the allelic (OR = 1.67, 95% CI 1.20-2.33, pperm < 0.01), additive (OR = 1.69, 95% CI 1.20-2.37, pperm < 0.01), dominant (OR = 1.81, 95% CI 1.15-2.87, pperm = 0.01) and recessive (OR = 2.34, 95% CI 1.15-4.73, pperm = 0.01) models. The association of the G rs1805087 allele of the MTR gene with the occurrence of FGR was also identified following the recessive model (OR = 3.01, 95% CI 1.05-8.68, pperm = 0.04). Conclusion: Our results indicated that maternal polymorphic loci rs1979277 SHMT1 and rs1805087 MTR may be associated with the development of FGR. Key words: Polymorphism, Associations, Fetal growth restriction, Folic acid

PRECLINICAL INVESTIGATION OF THE ALLERGENIC EFFECT OF THE DRUG BASED ON THE PHENOLIC COMPOUND KUD975

Introduction: Vascular endothelium is a cellular monolayer that covers the internal lumen of all blood vessels, thus separating blood from the vessel wall and tissues. The study of the role of endothelium in the pathogenesis of cardiovascular diseases led to an understanding of the concept of it as a target for the prevention and treatment of these pathologies. Research tasks: The purpose of this study was preclinical study of the allergic effect of the drug KUD975, based on a phenolic compound, which is a selective inhibitor of arginase 2. Methods: Experiments on the allergic properties of the phenolic compound KUD975, which is a selective inhibitor of arginase II, were carried out on albino sexually mature guinea pigs weighing 300 ± 20 g. The preparation was administered intragastrically as a suspension in a 1% starch paste using a specially prepared atraumatic probe at 0, 1 ml of suspension per 10 g of body weight of animals. As a control, we used data obtained in animals with intragastric administration of the corresponding volume of placebo-1% starch paste. Results: In the course of the study of the allergic properties of KUD975, when the reaction of active cutaneous anaphylaxis was formulated, it was found that the studied preparation in two and eight times daily therapeutic dosages did not possess allergic properties In the course of the study of the allergic properties of KUD975 in the formulation of a delayed-type hypersensitivity reaction, it was found that the study drug in two and eight times daily therapeutic dosages had no allergenic properties. Erythema, or, especially, infiltration and the appearance of ulcers at the site of administration as a resolving dose of the drug, as well as in the control of reactivity, were not observed in any animal participating in the experiment. Conclusion: When investigating the allergenic properties of the phenolic compound KUD975, which is a selective inhibitor of arginase II in the reaction of active cutaneous anaphylaxis, it was found that the study preparation in two and eight times daily therapeutic dosages does not have allergic properties. In the reaction of active cutaneous anaphylaxis in guinea pigs, the allergic properties of KUD975 in two and eight times daily therapeutic dosages were not detected Key words: compounds of phenolic nature, allergic action, endothelium, inhibitors of arginase I

Association of matrix metalloproteinase gene polymorphisms with different biological subtypes of breast cancer

Aim. To investigate the associations of matrix metalloproteinase (MMP) MMP3 (rs679620), MMP8 (rs1940475), and MMP9 (rs17576 and rs3787268) gene polymorphisms with different biological subtypes of breast cancer (BC). Materials and methods. The study sample consisted of 285 patients with BC of various biological subtypes (luminal A and B [n=153], triple negative [n=108], and HER2 positive [HER2+, n=24]) and 746 females in the control group. Genotyping of four polymorphic sites of MMP3 (rs679620), MMP8 (rs1940475), and MMP9 (rs17576 and rs3787268) genes was performed in the study groups. Results. The role of MMP gene polymorphisms in the BC development of various biological subtypes differs. The c.836 AG MMP9 polymorphism (rs17576, the odds ratio is 0.670.71 for the G allele) has a protective effect on the development of luminal A- and B-subtypes of BC; susceptibility to triple-negative BC is associated with the polymorphic site c.1331-163 GA MMP9 (rs3787268, OR 4.51 for genotype AA), and two polymorphisms of the MMP3 (c.133 TC, rs679620, OR 0.460.49 for T allele) and MMP8 (c.259 TC, rs1940475, OR 0.370.48 for T allele) genes are associated with HER2+ BC development. According to the in silico data, the above polymorphisms have pronounced functional effects in organs and tissues that are pathogenetically significant for the disease, including the target organ, the breast. Conclusion. The c.836 AG MMP9 (rs17576) polymorphism is associated with luminal A- and B-subtype of BC; c.1331-163 GA MMP9 (rs3787268) is associated with triple negative BC, and c.133 TC MMP3 (rs679620) and c.259 TC MMP8 (rs1940475) are involved in HER2+ BC development

Synergism between the N-acetyltransferase 2 gene and oxidant exposure increases the risk of idiopathic male infertility

N-acetyltransferase (NAT2) is a phase-II xenobiotic-metabolizing enzyme participating in the detoxification of toxic arylamines, aromatic amines and hydrazines. The present study was designed to investigate whether two common single-nucleotide polymorphisms (SNP) of the NAT2 gene (481C>T, rs1799929; 590G>A, rs1799930) are associated with susceptibility to idiopathic male infertility and to assess if the risk is modified by oxidant and antioxidant exposures. A total 430 DNA samples (203 infertile patients and 227 fertile men) were genotyped for the polymorphisms by PCR and restriction fragment length polymorphism. No association was found between the NAT2 polymorphisms and idiopathic male infertilit

The role of obesity in the implementation of genetic predisposition to the development of essential hypertension in men

BACKGROUND: Obesity is considered a non-infectious pandemic, and the increase in its spread is a serious medical and social problem. High values of body mass index closely correlate with arterial hypertension and its complications, but the effect of obesity on the realization of hereditary susceptibility to essential hypertension (EH) remains poorly understood. AIMS: To study the associations of polymorphic loci of MMPs with the development of EH in men depending on the presence of obesity. MATERIALS AND METHODS: The study was conducted in a case-control design. Surveyed 821 men – 564 patients with hypertension and 257 patients of the control group. Groups of patients and controls were divided into subgroups depending on the presence of obesity. All men were genotyped for eight polymorphic loci of MMPs. Nonsynonymous SNPs were detected using the software SIFT (https://sift.bii.a-star.edu.sg/). The regulatory potential was studied using the HaploReg service (https://pubs.broadinstitute.org/mammals/haploreg/haploreg.php). The association of SNPs with the expression level was detected using GTEx-portal (http://www.gtexportal.org). RESULTS: It was found that in obese men allele A (OR=2.01; p=0.01) and genotype GG (OR=0.42, p=0.01) of rs11568818 MMP7 are associated with the essential hypertension. In men without obesity allele 6A (OR=1.32; p=0.04) of rs3025058 MMР3 and genotypes GG (OR=1.52; p=0.04) and GA (OR=0.63; p=0.03)) of rs17577 MMP9 are associated with the development of the disease. These SNPs located in region of promoter and enhancer histone marks, in the region of hypersensitivity to DNAse-1, in binding sites of regulatory proteins and transcription factors. These SNPs associated with the level of gene expression. CONCLUSIONS: In this study we established associations with the development of EH of SNP rs11568818 MMP7 in obese men and of SNPs rs3025058 MMР3 and rs17577 MMP9 in non-obese men

Special Issue: “Genes and Human Diseases”

Studying mechanisms of development and the causes of various human diseases continues to be the focus of attention of various researchers [...

Estimation of candidate genes in the development of a combination of endometrial hyperplasia and uterine fi broids

Objective: the study of bioinformatics by six genetic polymorphisms (rs1782507, rs555621, rs7753051, rs887912, rs6732220, rs4986938) in the formation of a combination of endometrial hyperplasia with uterine myoma in women in the Central region of Russia. Materials and methods: the study group consisted of 1151 employees, including 170 patients with a combination of uterine fi broids with endometrial hyperplastic processes and 981 women in the control group without proliferative diseases of the pelvic organs. Material for the study were DNA samples isolated from venous blood by phenol-chloroform extraction.Analysis of the investigated polymorphisms was carried out by the detection ATK-man probes using real-time PCR. Results: risk factors for the development of a combination of endometrial hyperplasia and uterine fi broids combination of molecular genetic markers with rs673220, and rs4986938 and G rs887912 (ОR = 1.70), with rs6732220 and rs555621, g rs887912 (ОR = 1.53) and C rs1782507 T rs7753051 and rs887912 G (ОR = 1.40). Conclusion: the obtained data testify to the signifi cant contribution of combinations of polymorphic variants rs1782507, rs555621, rs7753051, rs887912, rs6732220 and rs4986938 to the formation of a combination of endometrial hyperplasia and uterine fi broids among women in the Central region of Russia

Polymorphisms of the TNF, LTA, and TNFRSF1B genes are associated with onsets of menarche and menopause in US women of European ancestry

Background The TNF, LTA and TNFRSF1B genes have been implicated in various traits related to menarche and menopause. Aim To analyse the TNF, LTA and TNFRSF1B genes for their association with ages at menarche (AM) and natural menopause (ANM). Subjects and methods The study sample consisted of 314 unrelated females of European ancestry. Twenty SNPs located in and near the genes were analysed using various statistical methods. In addition, the functional significance of the loci associated with AM and ANM was analysed in silico. Results Locus rs2229094 of the LTA gene was associated with AM according to the additive (β = −0.295, pperm = 0.016) and recessive (β = −0.940, pperm = 0.016) genetic models. Haplotype GG rs1148459-rs590368 of the TNFRSF1B gene was associated with AM (β = 0.307, pperm = 0.023). Haplotype GCA rs2844484-rs2229094-rs1799964 was associated with ANM after adjustment for covariates (β = −1.020, pperm = 0.035). All studied loci were associated with ANM after adjustment for breastfeeding (raw p < 0.05). In addition, eight of the most significant models of interlocus interactions were associated with AM and five with ANM. Conclusion The results of the present study suggest that the TNF, LTA and TNFRSF1B genes are associated with AM and ANM