Genetic determination of arterial hypertension in diabetes mellitus is complex and multifactorial, but given the key role in the pathogenesis of arterial hypertension, renin-aldosterone system and endothelial dysfunction, the genes responsible for the synthesis of protein components of the renin-angiotensin are of particular interest systems (RAS) . The main components of RAS are angiotensinogen (ATG), angiotensin-converting enzyme (ACE), and angiotensin II type 1 vascular receptor (AT1P). Numerous polymorphic markers were found within their genes, many of which were used in genetic analysis of hereditary diseases. As a result of numerous studies, association with the development of arterial hypertension in diabetes mellitus type 2 of the angiotensinogen gene, located on chromosome 1g 42-g 43, was demonstrated. exon. These are nucleotide substitutions leading, in turn, to the replacement of threonine by methionine in the 235th (M235T) and 174th (T174M) positions of the amino acid sequence.Family analysis and population studies showed the linkage of molecular variants of ATG, carrying threonine-235 and methionine-174, with arterial hypertension in representatives of different races. In the Moscow population, a link was found between the T174M AGT polymorphism and the development of arterial hypertension, myocardial infarction, and hypertofical cardiomyopathy. At the same time, the M allele and the MM genotype increased the risk of developing cardiovascular pathology, and the T allele and TT genotype, on the contrary, showed a protective effect.At the same time, the M allele and the MM genotype increased the risk of developing cardiovascular pathology, and the T allele and TT genotype, on the contrary, showed a protective effect.At the same time, the M allele and the MM genotype increased the risk of developing cardiovascular pathology, and the T allele and TT genotype, on the contrary, showed a protective effect.
To date, a wealth of data has been accumulated on the association of the polymorphism of the ACE gene with hypertension, myocardial infarction, left hypertrophy ventricle and other vascular complications of diabetes, as well as hypertrophic cardiomyopathy. For example, when examining a sufficiently large population (3145 people) in the framework of the Frimingham study, it was found that the presence of the D allele of the ACE gene is associated with a higher level of blood pressure in men, the D-allele association is especially pronounced with the level of diastolic pressure. For women, such patterns were not found. There is evidence that in hypertensive patients with the D allele of the ACE gene, the risk factor for coronary heart disease is a higher level of blood pressure and a higher pulse pressure than in patients with a protective I allele. There is evidence of the association of an ACE gene polymorphism with hypertension and in the Chinese population of u. There are a number of works in which the D-allele of the ACE gene is associated with the development of left ventricular hypertrophy. Thus, it was shown in the works that patients suffering from arterial hypertension, homozygous for the D-allele of the ACE gene, have a greater mass of the left ventricular myocardium than patients with genotype I / I.
In a number of papers, the authors try to establish a link between the effectiveness of ACE inhibitor therapy and the ACE gene genotype. Thus, M. Sasaki (1996) showed regression of left ventricular hypertrophy during treatment with an ACE inhibitor (enalapril). The study of changes in the activity of this enzyme in patients with various forms of cardiovascular pathology will allow to explore the pathways of AII formation in the process of the onset and development of diseases.
The data on the association of the ACE gene polymorphism with endothelial dysfunction, as well as the processes of remodeling of the vascular wall and atherogenesis are interesting.
An increase in local (local) endothelial ACE activity is associated with impaired endothelium-dependent vasodilation for acetylcholine in rats with hereditary hypertension. This suggests that local ASA hyperactivity can lead to endothelial dysfunction. Attempts to associate endothelial dysfunction with the ACE genotype (ACE) are based on this. In a study of H. Buikema (1994), endothelium-dependent vasodilation of the internal thoracic artery of a person obtained in CABG surgery in 34 patients was studied. It was shown that patients with the D / D genotype had a higher basal level of NO and a smaller capacity of excretion of stimulated NO than patients with genotype I / I. For patients with the D / D genotype, a higher level of local conversion of angiotensin I to angiotensin II is also characteristic.