Arterial hypertension is associated with the DNase I single nucleotide polymorphism Q222R and enhanced neutrophil extracellular trap formation

Aim. To study the association of single nucleotide polymorphism rs556621 (G> T) with development of stroke in patients of the East Siberian population with cardiovascular pathology and risk factors.Material and methods. The study involved 260 patients (157 men and 103 women) with stroke (mean age 57.0 [51.0-62.0]) and 272 patients (170 men and 102 women) of the control group (mean age 55.0 [51.0-62.0]). The examination of the main group included: collection of complaints, anamnesis, clinical examination, computed tomography of the brain, electrocardiography, echocardioscopy, ultrasound duplex scanning of extracranial brachiocephalic arteries, daily blood pressure and heart rate monitoring, analysis of the blood coagulation system. The patients of the main group have arterial hypertension, paroxysmal supraventricular tachycardias, dyslipidemia, atherosclerosis of the brachiocephalic arteries, disorders of the hemostatic system. The control group was studied in the framework of the HAPIEE international project. Molecular genetic research was performed by real-time polymerase chain reaction.Results. There were no statistically significant differences in the frequencies of genotypes and single nucleotide polymorphism rs556621 alleles (G>T) in the subgroup of patients with stroke and those in the control group. The frequency of the rare TT genotype among patients with stroke was 13.3%±4.16, among healthy individuals – 8.8±3.37% (p=0.1). Gender differences when comparing the frequencies of genotypes and alleles were also not detected (p>0.05). The frequencies of the TT genotype were approximately the same in the subgroup of patients with arterial hypertension (13.1%±4.22) and in the control group (7.4±5.25%; p>0.05). No significant differences were observed in the frequencies of the rare genotype of the studied polymorphism in the subgroup of patients with supraventricular tachycardias (20.0±14.37%), hypercoagulability (15.9±7.64%) and the control group (8.8±3.37%), p>0.05. A statistically significant relationship was found between the rare genotype TT of single nucleotide polymorphism rs556621 (G>T) and the development of stroke in patients with dyslipidemia and atherosclerotic lesions of the coronary arteries (p=0.041; odds ratio 1.86, 95% confidence interval 1.02-3.41).Conclusion. The genotype of TTs of single nucleotide polymorphism rs556621 (G> T) increases the risk of developing stroke in patients with dyslipidemia and atherosclerosis of the brachiocephalic arteries compared with carriers of the GG and GT genotypes. The obtained data are recommended to be considered when prescribing lipid-lowering and antithrombotic therapy.

Download Full-text

A Functional Single-Nucleotide Polymorphism in theTRPC6Gene Promoter Associated With Idiopathic Pulmonary Arterial Hypertension

Circulation ◽

10.1161/circulationaha.108.782458 ◽

2009 ◽

Vol 119 (17) ◽

pp. 2313-2322 ◽

Cited By ~ 129

Author(s):

Ying Yu ◽

Steve H. Keller ◽

Carmelle V. Remillard ◽

Olga Safrina ◽

Ann Nicholson ◽

...

Keyword(s):

Single Nucleotide Polymorphism ◽

Pulmonary Arterial Hypertension ◽

Arterial Hypertension ◽

Idiopathic Pulmonary Arterial Hypertension ◽

Nucleotide Polymorphism ◽

Single Nucleotide ◽

Functional Single Nucleotide Polymorphism ◽

Pulmonary Arterial

Download Full-text

New Drugs and Emerging Therapeutic Targets in the Endothelin Signaling Pathway and Prospects for Personalized Precision Medicine

Physiological Research ◽

10.33549/physiolres.933872 ◽

2018 ◽

pp. S37-S54 ◽

Cited By ~ 5

Author(s):

A. P. DAVENPORT ◽

R. E. KUC ◽

C. SOUTHAN ◽

J. J. MAGUIRE

Keyword(s):

Single Nucleotide Polymorphism ◽

Pulmonary Arterial Hypertension ◽

Arterial Hypertension ◽

Precision Medicine ◽

Small Molecule ◽

Rapid Expansion ◽

Nucleotide Polymorphism ◽

Single Nucleotide ◽

Endothelin 1 ◽

Pulmonary Arterial

During the last thirty years since the discovery of endothelin-1, the therapeutic strategy that has evolved in the clinic, mainly in the treatment of pulmonary arterial hypertension, is to block the action of the peptide either at the ETA subtype or both receptors using orally active small molecule antagonists. Recently, there has been a rapid expansion in research targeting ET receptors using chemical entities other than small molecules, particularly monoclonal antibody antagonists and selective peptide agonists and antagonists. While usually sacrificing oral bio-availability, these compounds have other therapeutic advantages with the potential to considerably expand drug targets in the endothelin pathway and extend treatment to other pathophysiological conditions. Where the small molecule approach has been retained, a novel strategy to combine two vasoconstrictor targets, the angiotensin AT1 receptor as well as the ETA receptor in the dual antagonist sparsentan has been developed. A second emerging strategy is to combine drugs that have two different targets, the ETA antagonist ambrisentan with the phosphodiesterase inhibitor tadalafil, to improve the treatment of pulmonary arterial hypertension. The solving of the crystal structure of the ETB receptor has the potential to identify allosteric binding sites for novel ligands. A further key advance is the experimental validation of a single nucleotide polymorphism that has genome wide significance in five vascular diseases and that significantly increases the amount of big endothelin-1 precursor in the plasma. This observation provides a rationale for testing this single nucleotide polymorphism to stratify patients for allocation to treatment with endothelin agents and highlights the potential to use personalized precision medicine in the endothelin field.

Download Full-text