Ethno-Territorial Distribution of the C174M and C235T Polymorphisms of the AGT Gene and C677T of MTGFR Gene in the Population of the Azerbaijan Republic

The prevention of hereditary diseases associated with gene and chromosomal disorders, in particular multifactorial-polygenic diseases is one of actual areas of medical genotyping. For the first time in the population of the Republic of Azerbaijan we have identified mutations C174T and C235T of the angiotensinogen gene and mutation C677T of the methylenetetrahydrofolate reductase gene both in the control group and among patients with diseases of the cardiovascular system. Reliable connections for the frequency of occurrence of polymorphism of the C174T and C235T alleles of the angiotensinogen gene and polymorphism of the C677T allele of the methylenetetrahydrofolate reductase gene were found with a statistical method. To identify the ethno-geographic relationship of the mutations C174T and C235T of the AGT gene for the population of the Azerbaijan Republic, we examined practically healthy individuals and patients with CVD. The composition of this group was multinational and corresponded to the main national and ethnic composition of the Republic. The distribution of the identified mutations C174T and C235T of the AGT gene, as well as the C677T polymorphism of the MTHFR gene among ethnic groups of the Azerbaijan Republic is identified as uneven.

Precision Medicine in the Renin-Angiotensin System: Therapeutic Targets and Biological Variability

Pathologies linked to the renin-angiotensin system are frequent, and the drugs used in them are numerous and show great variability in therapeutic effects and adverse reactions. Genetic variants have been detected in the angiotensinogen gene (6), angiotensin-converting enzyme (9), angiotensinconverting enzyme 2 (1), and angiotensin receptor Type 1 (4) among others. However, the large number of studies that have analyzed each of them makes it complex and almost impossible to consider all the existing information. This manuscript aims to review the effects of the different known variants on the expected response of different drugs as a basis for the future development of therapeutic guidelines that seek to implement therapeutic individualization strategies on the renin-angiotensin system.

Abstract 12717: Enhance Negative Modulation of Beta 3 -Adrenergic Stimulation on Cardiomyocyte Functional Performance, [Ca 2+ ] i Regulation and β-Adrenergic Reserve in Rats Expressing Human Angiotensinogen Gene

Background: Transgenic rats expressing the human angiotensinogen gene [TGR (hAogen) 1623] (hAogen) exhibit sustained hypertension and systolic dysfunction associated with altered cardiac renin-angiotensin system and β- adrenergic receptor (AR) signal transduction systems. We have shown previously, in contrast to β 1 - and β 2 -ARs, β 3 -ARs are linked to G i proteins, and stimulation of β 3 -ARs inhibits cardiac contraction and relaxation. Hypertension is associated with increased cardiac expression of G i proteins. This may alter β 3 -AR stimulation and play an important role in the cardiac functional impairment of this humanized model of hypertension. However, the alteration and functional effect of β 3 -AR activation in this model are unknown. We tested the hypothesis that high cardiac tissue Ang II content in hAogen may cause an up-regulation of cardiac β 3 -AR, which exacerbates myocyte dysfunction and impairs calcium regulation, thereby directly contributing to the cardiac dysfunction. Methods: We compared LV myocyte β 3 -AR expression and myocyte functional and [Ca 2+ ] i transient ([Ca 2+ ] iT ) responses to β- and β 3 -AR stimulation in myocytes obtained from 8 Sprague Dawley (SD) control and 8 hAogen male adult rats. Results: Versus SD, in hAGT rats, basal myocyte contraction (dL/dt max , 107.1 vs 138.8 μm/s), relaxation (dR/dt max , 94.0 vs 103.9 μm/s) and [Ca 2+ ] iT (0.15 vs 0.21) were depressed. A non-selective β-AR agonist, isoproterenol (ISO) (10 -8 M) produced significantly smaller increases in dL/dt max , (42% vs. 61%), dR / dtmax (35% vs. 51%), and [Ca 2+ ] iT (20% vs. 30%). Moreover, versus SD, in hAogen rats, LV myocyte β 3 -AR protein level increased by 32% (0.29 vs 0.22) with resulted significantly altered myocyte functional response to β 3 -AR stimulation. Compared with the changes in SD myocytes, in hAogen myocytes, BRL (10 -8 M) produced a significantly greater decreases in dL/dt max , (27% vs 12%), dR/dt max (28% vs 11%), and [Ca 2+ ] iT (17% vs 10%). Conclusions: TGR (hAogen) 1623, this humanized model of hypertension is associated with an up-regulation of LV myocyte β 3 -AR, which enhances β 3 -AR-caused inhibition of myocyte contractile, relaxation and [Ca 2+ ] iT and exacerbates β-AR desensitization, thereby directly contributing to the cardiac dysfunction.

Association of mononucleotide polymorphisms of angiotensinogen gene at promoter region with antihypertensive response to angiotensin receptor blockers in hypertensive Chinese

Introduction: This study aimed to investigate whether mononucleotide polymorphisms of the angiotensinogen gene at promoter were associated with the blood-pressure-lowering response to telmisartan treatment. Materials and methods: After a two-week single-blind placebo run-in period, 148 patients with mild-to-moderate primary hypertension received monotherapy with 80 mg/day of telmisartan and then were followed up for eight weeks. The -6A/G and -20A/C polymorphisms of the angiotensinogen gene at promoter were determined through polymerase chain reaction and restriction fragment length polymorphsim analysis. The relationship between these polymorphisms and changes in blood pressure was observed and evaluated after eight weeks of treatment. Results: There were no significant differences between -6A/G, -20A/C polymorphisms of the angiotensinogen gene and blood pressure reductions after treatment, p>0.05. Conclusion: It is suggested that angiotensinogen-6 A/G and angiotensinogen-20 A/C polymorphisms were not associated with the antihypertensive response to telmisartan treatment in Chinese patients with hypertension.