REVIEW
DNA methylation is a fundamental epigenetic modification mechanism that plays a significant role in gene activity regulation and underlies the development of various diseases. In this article, we have focused on analyzing the genome-wide studies results of DNA methylation in fetal growth restriction (FGR), which reported the identification of differentially methylated regions or genes using high-throughput technologies. Analysis of the included studies has revealed significant alterations in DNA methylation patterns in FGR, affecting 1,022 differentially methylated genes (DMGs), which are overrepresented in the processes of the immune response, the PI3K/AKT/mTOR and MAPK signaling pathways. Among these, only 4% of DMG are replicated between studies. These genes are associated with the signal transduction, cellular morphogenesis, nervous system development and cell adhesion. Additionally, we have identified a cluster of genes that not only exhibited differential methylation in placental tissue but also showed statistically significant changes in gene expression in FGR. These common genes and their products are involved in cell-cell interaction, cell migration, cytoskeleton organization, apoptosis, and nervous system development. The obtained data indicate that certain patterns of DNA methylation associated with the FGR development in the prenatal period may be the basis for increased susceptibility to diseases such as diabetes mellitus, obesity, pathologies of the bronchopulmonary system and immunological dysregulation in later life. The results of our work highlight the important role of a comprehensive analysis of DNA methylation and gene expression for the study of the genetic component underlying FGR.
The prevalence of obesity in the Russian Federation continues to increase. Thus, among men, the prevalence increased from 10.8% in 1993 to 27.9% in 2017, among women – from 26.4% to 31.8%, respectively. Large-scale resources of genetic/genomic data, as well as objective reviews of genetic/genomic variants in cohorts of people with early development of obesity, especially in inbred populations, have led to the identification and characterization of rare and common genetic variants associated with the development of obesity. The increasing understanding of the prevalence of obesity caused by rare variants of the nucleotide sequence, as well as the identification of new genes associated with monogenic obesity, emphasize the importance of genetic analysis in assessing the cause of the disease. Most of the genes discussed in the review are involved in the leptin and melanocortin production system, however, genes regulating adipogenesis can also influence the development of obesity. Special attention should be paid to genetic testing of people with earlyonset severe obesity, especially in cases where it is accompanied by dysmorphic disorder, disorders of the nervous system or other systemic abnormalities. This testing can help in the accurate diagnosis and understanding of the causes of obesity, which, in turn, will allow the development of more individualized treatment strategies. The use of methods such as antisense oligonucleotides and gene editing technologies can significantly change treatment approaches, making them more effective.
ORIGINAL RESEARCH
Background. Acute respiratory viral infection (ARVI) is one of the pressing medical and socio-economic problems, frequently occurring in all age groups worldwide. The most important viral etiologic agents are respiratory syncytial virus (RSV) and influenza virus. TLR4 is an innate immune receptor on the cell surface that recognizes pathogen-associated molecular patterns (PAMPs), including viral proteins, and triggers the production of type I interferons and proinflammatory cytokines to fight infection. Many studies have reported the effect of TLR4 Asp299Gly and Thr399Ile polymorphisms on the risk of developing ARVI, but no definitive conclusions have been made.
Aim: to investigate the association between the rs4986790 and rs4986791 polymorphisms of the Toll-like receptor (TLR4) gene and the development of ARVI.
Methods. A systematic literature search was performed using the PubMed, Google Scholar Search, and Russian Science Citation Index (RSCI) databases according to PRISMA 2020 guidelines. Pooled odds ratios with corresponding 95% confidence intervals were calculated for five genetic models. Data processing and construction of forest plots to assess the pooled results were performed in RevMan 5.4.
Results. The meta-analysis included 9 publications on the rs4986790 polymorphism and 5 on the rs4986791 polymorphism, that met the inclusion/exclusion criteria. Most of the articles combined studies of both polymorphisms. The sumple size of the main group for Asp299Gly was 1228, the control group – 8694, for Thr399Ile – 629 and 2858, respectively. The results included in the meta-analysis did not have significant heterogeneity among studies for all genetic models. The analyzed data showed that the studied polymorphisms were not associated with the risk of ARVI.
Conclusions. The study may be useful for better understanding the exact role of each component of innate and adaptive immunity in ARVI. These data, summarizing the positive, negative or absent correlation between ARVI and gene polymorphisms, provide important information on the mechanisms of viral infection and can help in the development of new vaccines and pharmacological treatment.
Background. Hepatolenticular degeneration (HLD) is a degenerative disease caused by variable causal mutations in the ATP7B gene. It is difficult to overestimate the importance of developing rapid and accurate approaches to diagnosing this disease at early stages. Studying the dependence of clinical manifestations of HLD on the type of mutations in the ATP7B gene allows us to select diagnostic criteria for the pathology.
Objective: to study manifestations of hepatolenticular degeneration (HLD) in 100 residents of Primorsky Region with genetically confirmed neurological forms of the disease.
Methods. Molecular genetic study conducted using Sanger sequencing; neuropsychological – using the MOCA, HADS scales.
Results. It was found that in the spectrum of mutations of the ATR7B gene, the emerging positions include two groups of mutations, one of which is typical for HLD patients in the western regions of our country, the other – for HLD representatives of the Asia-Pacific region. The maximum (80%) occurs with four mutations: p.His1069Gln, Glu1064Lys, c.2304insC and Gly710Ser. The main clinical symptoms of the diseases are motor defects of extrapyramidal origin and mental changes that form a cognitive deficit.
Conclusions. Statistical consistent signals in the manifestations of HLD in patients with different character changes. The peculiarity of HLD is the dynamics of its diseases, indicating the transformation of neurotic diseases into neuroautonomic imbalance. Its detection during genetic detection of one of the four main mutations in the homozygous state allows to correct the early diagnostics of HLD.