Essential hypertension and genes. Atherosclerosis and genetics. Bronchial asthma and genes

Essential hypertension (EG) is a heterogeneous group of diseases, the main clinical manifestation of which is an increase in blood pressure and related complications (heart attacks, strokes, renal failure). To date, more than [00 genes are known whose products can directly or indirectly participate in the complex pathogenesis of various forms of EG. First of all, these are components of the renin-angiotensin and kallikrein-kinin systems; products that ensure vascular tone (endothelin, nitrous oxide synthase, calcium channel components) and vascular structure (elastin, fibrillin, collagen-binding protein); adrenergic system receptors (e.g., dopamine); metabolic products of steroid hormones (11-hydroxylase, 17-a-hydroxylase, etc.) and water-salt homeostasis (aquaporins, vasopressin receptors, ion channels). However, the study of the polymorphism of the corresponding genes did not reveal particularly significant associations of some of them with various clinical variants of essential hypertension. The main candidate genes involved in the predisposition to EG are presented in the table. It has been shown that a number of genes that form a predisposition to essential hypertension contribute to the etiology of another widespread disease – atherosclerosis. This is due to the similarity of a number of pathogenetic mechanisms of these diseases, in particular, due to impaired functioning of the renin-angiotensin and kallikrein-kinin systems. However, the leading role in the pathogenesis of atherosclerosis is given to increasing the concentration of lipids in blood plasma, impaired blood coagulation and the integrity of the vascular wall. In this regard, genes whose products provide lipid metabolism are considered as the main candidate genes. Significant linkage of the disease was found with a number of loci: CERT (transport protein of cholesterol esters on chromosome 16), with aroA1 / apoC3 / aroA4 cluster on chromosome 11. In another common multifactorial disease – bronchial asthma – a significant number of loci linked to the disease in various families, candidate genes are localized, the products of which can be involved in three main parts of the pathogenesis of the disease: immunological, inflammatory and neurogenic. Particular attention is paid to the genes of the family of interleukins, cytokines and cytokine receptors, which ensure the normal functioning of the bronchial mucosa and mast cells that control the level of IgE in the blood and detoxification of xenobiotics. Given the significant role of impaired functioning of the immune system in various forms of bronchial asthma and other forms of atopy, the identification of associations of these diseases with the main histocompatibility complex (HLA) is still of great importance. The most likely candidates for the role of the “main gene” for predisposition to bronchial asthma are the interleukin-9 and interleukin-4 genes mapped to chromosome 5q31-q33. Along with this, it was shown that for a number of variants of bronchial asthma that begin in childhood and are accompanied by an increase in the concentration of IgE in the blood, a significant association with the locus of chromosome 20p13 is found, where the gene of the membrane-associated protein of cell surfactant from the family of cytokines / cytokine receptors is localized. It is assumed that in addition to the two indicated genes, several more genes localized in the chromosomal regions – 6p21.3 – p21.1 (TNFA), Hql2-q13 (IGEL and FCERlb), 12ql5-q24, play a significant role in the formation of a genetic predisposition to this disease. 1 (IGIF and NOS1), 13ql4.2-ql4.3 (ESD). The products of these genes are: tumor necrosis factor, a protein that controls the level of total IgE, an immunoglobulin mast cell receptor, interferon, neural nitric oxide synthetase and esterase D, respectively. A number of genes have been identified that exhibit adhesion to other common multifactorial diseases, such asrheumatoid arthritis, multiple sclerosis, osteoporosis, obesity, endometriosis, etc. However, despite the success in searching for associations and linking to specific gene loci, it is currently impossible to identify a spectrum of genes for screening for predisposition for any disease with a hereditary predisposition. There are several reasons for this; pronounced genetic heterogeneity of BNP, differences in the mechanisms of genetic predisposition in familial and sporadic cases, differences in the frequency of occurrence of alleles of predisposition genes between populations, as well as a relatively small contribution to the pathogenesis of the disease products associated with the disease genes. Thus, neither the use of mathematical models of the inheritance of multifactorial diseases, nor the methods of DNA analysis yet allow us to obtain adequate figures for the repeated risk of the disease in relatives of affected probands, which could be used for all families from different populations.

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