Genetic Risk Factors for the Development of COVID-19 Coronavirus Infection.

The COVID-19 coronavirus pandemic has spread to 215 countries around the world and caused tens of millions of infections and more than a million deaths worldwide. In the midst of COVID-19 infection, it is extremely important to identify new protein and gene targets that may be highly sensitive diagnostic and prognostic markers of the severity and outcome of the disease for combating this pandemic. Identification of individual genetic predisposition allows personalizing programs of medical rehabilitation and therapy. It has now been shown that the transmissibility and severity of COVID-19 infection can be affected by gene variants in both the human body (ACE2, HLA-B*4601, FcγRIIA, MBL, TMPRSS2, TNFA, IL6, blood group A antigen, etc.) and the virus itself (ORF8 in RNA polymerase, ORF6 in RNA primase, S, N, E proteins). The presence of mutations in the proteins of the virus can change the affinity and specificity for the binding of targeted drugs to them, being the molecular basis of individual differences in the response of the human body to antiviral drugs and/or vaccines. The review summarizes the data on the variants of the genomes of the coronavirus and humans associated with an individual predisposition to an increased or decreased risk of transmission, severity, and outcome of COVID-19 infection. Targeted drugs and vaccines being developed for the therapy of COVID-19 infection are briefly reviewed.

X-linked and autosomal dominant forms of the ichthyosis in coinheritance.

According to modern classification, there are two forms of inherited ichthyoses: syndromic and non-syndromic, each of them consists of more than ten different nosologies. The commonest types of the ichthyosis are X-linked recessive (prevalence 1/2000-6000 in men) and autosomal dominant, or ichthyosis vulgaris with incomplete penetrance (1/250-1000). The X-linked form is associated with mutations in steroid sulfatase STS gene, it is noteworthy that there is a full deletion of the gene in 90% of cases. Ichthyosis vulgaris is caused by heterozygous mutations in the FLG gene encoding filaggrin. It is important to note that the clinical forms of these diseases are indistinguishable. The aim of this study was to search for pathogenic or likely pathogenic mutations which are associated with various forms of the inherited ichthyosis such as other inherited diseases with similar phenotypic signs. The sequencing was done on a HiSeq 4000 sequencer (Illumina) by paired-end reading (2 × 150 bp). The identified mutation p.Arg2037Ter in the heterozygous condition has been described before in databases as being pathogenic. Also, our patient has a full deletion of the STS gene and it was found that our patient carries two pathogenic mutations which are related to different forms of the inherited ichthyosis.

[Genetic and epigenetic news in gerontology].

The overview represents the recent most conspicuous findings in aging studies. It includes new data on the whole genome association studies (GWAS) in big cohort of centenaries, recently found mutation protecting from Alzheimer disease, discovery of hypothalamus as a command center of human aging, very important data on the negative effect of common antioxidants in the treatment of lung cancer as well as new data concerning antiaging and anticancer effects of common drugs such as rapamycine and metformin. Substantial part of the review is devoted to the epigenetic problems of senescence and feasible impact of basic epigenetic mechanisms (methylation of DNA and histone proteins, DNA heterochromatization) in regulation of gene expression, long-term genome reprogramming during early childhood, and transgeneration transmission of epigenetic traits. The necessity of transition from molecular studies of dormant human genome (anatomy of human genome) to genome in action (dynamic genome) and thus with special emphasis to epigenetic medicine is stressed.

[Frequency of some diseases and conditions in geriatric patients with coronary heart disease and various genotypes of transcription factor 7-like 2 protein].

In 2009-2010, 98 patients diagnosed with the coronary heart disease, but without the expressed metabolic violations, decompensated conditions and diseases were surveyed. Patients of 60-90 years were divided by age into two groups: younger than 75 years--47 people; 75 years and older--51; there were 41 women and 57 men; the ratio between women and men was 1:1.4; average age was 76.0 ± 1.3 years. The average age of women was 76.0 ± 1.8 years, men--76.1 ± 2,0 years. 96.0 ± 2.0% of geriatric patients with CHD complained of steno-cardiac pains in pre-cardiac area; the excess mass of a body was observed in 43.4 ± 5.0% of geriatric patients with CHD, acute myocardial infarction in the anamnesis was noted in 52.5 ± 6.9% (n = 52); hypertensive illness had 98.0 ± 1.4% (n = 97). Patients had the favorable average levels of lipoproteins of high density (not lower than 1 mmol/l). A significant number (79.2 ± 5.6%) of patients had hemodynamically significant narrowing of coronary vessels (75% and more), while the area of myocardial hypokinesia was observed in 41.2 ± 6.9% of patients, sharp violation of brain blood circulation was noted in 14.1 ± 9.8%. Wild type homozygous genotype of TCF7L2 gene was detected significantly more often (77.6 ± 4.7%) in patients of advanced and senile age with CHD, regardless of age group, exis-tence of accompanying diseases and conditions, such as previous myocardial damage, acute disorders of cerebral circulation and fatty degeneration of the liver. However allele of risk T (totally C/Tand T/T) of TCF7L2 gene came to light in 22.4 ± 9.1% of geriatric patients with CHD, that contributes to development of a metabolic syndrome in such patients and reduces term of their life.

[Genotype and allele frequencies of UCP and PPAR gene families in residents of besieged Leningrad and in the control group].

Genotype and allele frequencies of uncoupling proteins 2 and 3 genes (UCP2 and UCP3) and peroxisome proliferator-activated receptors genes (PPARA, PPARD and PPARG) were studied in 206 residents of the siege and in 139 individuals of more than 69 years old (control group). Studied polymorphisms included UCP2 (Ala55Val), UCP3 (C-55T), PPARA (G/C), PPARD (+294T/C), and PPARG (Pro12Ala). The G allele and the G/G genotype (PPARA) were overrepresented in the group of survivors and C/C (UCP3) genotype prevailed in the women of besieged Leningrad compared to relevant control groups of the persons of the same age who did not suffered hungry disaster. Feasible protective effects of PPARA gene allele G and C allele of UCP2 genes are briefly discussed.

[Genomic of aging and predictive medicine].

New molecular-genetic methods stimulate substantial advances in complex diseases studies, speed up identification of new candidate genes participating in functional genetic modules (gene nets) associated with many common diseases. Decisive impact of predictive genetic studies in efficient implementation of genomic technology advances into presymptomatic identification of the subjects of high risk groups prone to various common complex diseases is reviewed. Substantial progress of genomic studies in genetic of aging processes, including complex metabolic processes and gene regulation is outlined. Advances of predictive medicine in pharmacogenomic, nutrigenomic, sport genomic as well as in genomic of aging substantiate real and soon progress in promotion active healthy longevity.

Genetic determinants of the efficiency of climatotherapy in patients with chronic heart failure.

We studied the dependence of climatotherapy effectiveness in patients with chronic heart failure (functional classes 0-II) on Ca(2+)-ATPase, phospholamban, beta1-adrenoceptor, and insulin-like growth factor 1 gene polymorphisms and possible interaction of these genes during the realization of the effect of climatotherapy. The effectiveness of climatotherapy depended on polymorphism of the studied genes; the maximum effect was attained in patients with the GG polymorphism of the Ca(2+)-ATPase gene, GT polymorphism of the phospholamban gene, ArgGly polymorphism of the beta1-adrenoceptor gene, and 19/19 polymorphism of the insulin-like growth factor 1 gene. We demonstrated additive interaction of Ca(2+)-ATPase and beta1-adrenoceptor genes during the realization of the cardiotonic effect of climatotherapy.

[Genetic polymorphism and aging].

The review of the modern conceptions concerning a role of genetic factors in processes of ageing and longevity is presented. Despite of the various hypotheses explaining mechanisms of ageing, many aspects of this natural stage of life have not been studied yet. Ageing is a process which development is under the control of many endogenous (hereditary) and exogenous (environment) factors. Many questions of interaction of genes and their products-proteins among themselves and with environmental factors remain opened. Ethnic and geographical features of association of those or others polymorphic alleles with longevity and ageing are still not completely clear. Prolongation of the period of active longevity is possible via two methods: by means of modulation of activity of the genes that influence directly on "speed of ageing" with the aid of introduction of geroprotectors protecting an organism from action of endotoxins, and by means of predictive diagnostics and preventive maintenance of frequent multifactorial diseases with the aid of testing polymorphisms in genes of "predisposition". Nowadays testing of the genetic markers which are responsible for hereditary predisposition to the most frequent multifactorial diseases and are the main reasons of ageing and "enemies" of active longevity is quite possible. The basic genes of "predisposition", genes of "ageing" and their polymorphisms are briefly reviewed and some results of testing of these genes are considered.