[The role of gene-gene and gene-environmental interactions of polymorphic matrix metalloproteinases loci in the formation of the risk of stroke in men with hypertension]. / Rol' gen-gennykh i genno-sredovykh vzaimodeistvii polimorfnykh lokusov matriksnykh metalloproteinaz v formirovanii riska razvitiya ishemicheskogo insul'ta na fone arterial'noi gipertenzii u muzhchin.

OBJECTIVE: Analysis of the role of genetic polymorphisms of matrix metalloproteinases (MMPs), their gene-gene and gene-environment interactions in the formation of ischemic stroke in men with arterial hypertension (AI). MATERIAL AND METHODS: The study included 523 men with arterial hypertension: 201 patients with ischemic stroke and 322 patients without stroke. The association of MMPs loci with stroke with hypertension was determined by logistic regression analysis in dominant, recessive, additive genetic models in PLINK v.2.050. For five SNPs co-located on chromosome 11 (314.3 kb), haplotypic analysis was performed, the relationship of haplotypes with stroke development was determined by the EM algorithm. Gene-gene and gene-environment interactions of MMPs with smoking and alcohol consumption during stroke development were evaluated by GMDR (Generalized Multifactor Dimensionality Reduction) using GMDR v.0.9 software. RESULTS: Polymorphic locus rs3025058 is associated with stroke in men in dominant and additive genetic models (OR=0.63-0.74, pperm=0.03). Four haplotypes of MMPs have a protective effect on the development of stroke with hypertension (OR=0.48-0.50, pperm=0.02-0.03). Four models of gene-gene interactions of polymorphic MMPs loci (OR=2.19-2.55, pperm<0.001) and three four-factor models of gene-environment interactions of MMPs with alcohol abuse (OR=2.82-3.11, pperm<0.001) are associated with a high risk of ischemic stroke in men with hypertension. rs3025058, rs1320632, rs11225395 and rs1799750 demonstrate the greatest contribution to gene-gene and gene-environment interactions in the formation of AI. CONCLUSION: Thus, the results of the study indicate that the interactions of MMPs genes with each other and with modifiable environmental factors play a significant role in the development of stroke with hypertension in men.

Investigation on the Association of Cardiovascular Markers with Severity of Chronic Pyelonephritis.

Chronic kidney disease (CKD) is an established independent risk factor for cardiovascular disease (CVD) and is caused by chronic pyelonephritis (CP). This study aimed to investigate the effect of the association of cardiovascular markers with the course of CP on the comorbidity of CP with ischemic heart disease. The study participants included 125 patients with CP without symptoms of urinary tract obstruction who were divided into three groups. The first group (n=45) consisted of patients with recurrent CP (CPr) three or more times per year. The second group (n=42) included patients with active phase pyelonephritis (CPa), with a frequency of two times or less per year, with concomitant pathology (stable coronary artery disease, functional class I - II), and the third group (n=38) included patients with an inactive phase of the disease (CPi), with a history of pyelonephritis of at least five years. The patients' carotid artery augmentation index (AI %) and the change in the diameter of the brachial artery (D %) in CPi, CPa, and CPr groups were 8.44±1.76, 15.47±4.00, 11.71±1.70, 13.81±3.06, 12.75±2.55 and 6.54±3.27, respectively. The left ventricular ejection fraction (EF) index in the three study groups was estimated to be 68.92±3.76, 64.76±2.75, and 66.28±3.45%, respectively. An analysis of the results showed the most significant changes in the parameters of the cardiovascular system in patients with a comorbid and relapsing course of CP. The results showed a significant increase in pulmonary artery diameter, EF, left ventricular pressure and volume, pulse wave velocity in the aorta, and vascular resistance index.

[Polymorphic locus rs1061624 of the ТNFR2 gene is associated with the development of arterial hypertension in males].

Aim To study the involvement of cytokine polymorphous loci in development of arterial hypertension (AH) in men from the Central Black Earth region of Russia.Materials and methods 821 men were evaluated, including 564 patients with AH and 257 individuals of the control group. Analysis of 8 cytokine mononucleotide polymorphisms (MNP) was performed using the real-time polymerase chain reaction with TagMan probes. Statistical analysis was performed with the STATISTICA (v.10.0) and PLINK (v.1.06) software. The regulatory potential of MNP was analyzed with the HaploReg (v.4.1) service (http://archive.broadinstitute.org).Results The rs1061624 ТNFR2 polymorphous locus was associated with development of AH in men in recessive (odd ratio (OR), 0.33; 95 % confidence interval (CI): 0.18-0.61, рperm=0.0004) and additive (OR, 0.50, 95 % CI: 0.34-0.74, рperm=0.0006) genetic models and exerted a protective effect in development of AH. The rs1061624 MNP of the ТNFR2 gene has a regulatory significance; it is located in the DNA sites hypersensitive to the action of DNAase 1 and in binding sites for transcriptional factors and histones that mark enhancers and promoters in different organs and tissues.Conclusion The rs1061624 ТNFR2 gene polymorphism is involved in the development of AH in men of the Central Black Earth region of Russia.

[The role of stress factors and genetic predisposition in the development of stroke in patients with essential hypertension]. / Rol' stressovogo faktora v realizatsii geneticheskoi predraspolozhennosti k razvitiiu insul'ta na fone gipertonicheskoi bolezni.

To study the interaction of polymorphic markers of matrix metalloproteinases (MMP) and chronic stress in the development of stroke associated with hypertension. MATERIAL AND METHODS: A total of 830 patients, including 303 patients with ischemic stroke associated with essential hypertension (EH) and 527 patients with EH without stroke, were examined. The study of metalloproteinases SNP was carried out using real-time PCR. The functional significance and influence of polymorphic loci on gene expression was studied using of HaploReg (v4.1) (http://archive.broadinstitute.org) and GTEx-portal (http://www.gtexportal.org). RESULTS AND CONCLUSION: An association of the genotype GG (rs11568818) of MMP7 with a high risk of stroke in patients exposed to regular stress (OR=1.71) was observed. It was found that allele 5A and genotype 5A/5A (rs3025058) of MMP3 had a protective effect on the development of stroke in patients without regular stress in the anamnesis (OR=0.73 and OR=0.60, respectively). Those SNPs are localized in the region of histone proteins H3K4me1 and H3K4me3, in the region of hypersensitivity to DNase-1, in the region of binding of regulatory proteins and transcription factors. The polymorphic locus rs11568818 is associated with the expression level of MMP7.

A highly emissive inorganic hexamolybdenum cluster complex as a handy precursor for the preparation of new luminescent materials.

The synthesis and characterisation of a new, highly luminescent inorganic cluster complex, (Bu4N)2[Mo6I8(NO3)6], are described. The complex possesses labile nitrato ligands and is therefore a useful precursor for the design of new luminescent materials. To exemplify this, functionalised polystyrene beads have been utilised as "polymeric ligands" to immobilise the molybdenum cluster complex.

[The role of genetic polymorphisms of interleukins in chronic lymphocytic leukemia in patients of different ages].

Chronic lymphocytic leukemia (CLL) is a multifactorial disease, in which development the important role played the cytokine genes, in particular interleukins. This type of leukemia is more common in the elderly. The purpose of the study was to evaluate the association of genetic polymorphisms of interleukin with the development of chronic lymphocytic leukemia among residents of the Central Chernozem region of Russia. Genotyping of the -889C/T IL-1A, -590C/T IL-4 and VNTR IL-1 Ra was conducted in 206 patients with CLL and 307 individuals of the control group. The study found that the genetic risk factor for the development of CLL is allele -590T IL-4 (OR=-1,45). The development of thrombocytopenia in patients with CLL is associated with genetic variants -889T IL-1A (OR=1,95), -889TT IL-1A (OR=6,2) and IL-1Ra*1 (OR=-2,32).

[Clinical associations of genetic variants of interleukins with the formation of chronic lympholeukemia in elderly patients].

We investigated association of polymorphisms of interleukin IA (IL-1A), interleukin 4 (IL-4), interleukin 5 (IL-5), interleukin-8 (1L-8) genes in elderly patients with predisposition to the development of chronic lym,nphocytic leukemia (CLL). Risk factor of chronic lymphocytic leukemia is a genetic variant -590T IL-4 (OR = 1,45) and protective factor -590S IL-4 (OR = 0,68). Genetic markers -590T IL-4 (OR = 2,46), -590TT IL-4 (OR = 6,65) and mix-590TT genotype of IL-4 allele 703S-IL-5 (OR = 6.70) were associated with stage 0-1 chronic lymphocytic leukemia whereas genetic markers -889T IL-1A (OR = 1,51), -703T IL-5 (OR = 1,52) and a combination of genotype -703ST IL-5 allele-251A IL-8 (OR = 2.85) were related to the development of stage II of the disease. Risk factor for the formation of II-IV stages of chronic lymphocytic leukemia is a genetic variant -703T IL-5 (OR = 1,95).

[Structural and functional changes in myocardium of patients with chronic heart failure treated with spironolactone].

The aim of the work was to study structural and functional characteristics of the left ventricle (LV) and diastolic function in patients with systolic chronic heart failure (CCF). Group 1 included 34 patients with LV systolic dysfunction (ejection fraction > 45%) treated with spironolactone (verospiron) at 25-50 mg/day. Group 2 of 30 untreated patients served as control. Echo CG was performed by routine method in the M-modal regime. Combination of diastolic (DD) and systolic (SD) dysfunction was documented in 20 (31.2%) patients, restrictive type in 27 (42.2%). Spironolactone had beneficial effect on structural and functional characteristics of myocardium. It significantly increased LV ejection fraction from 23.8 +/- 7.4% in the beginning of the study to 43.3 +/- 8.6% 12 months later (p < 0.05). During 12 month, patients with systolic CCF showed positive dynamics of LV diastolic dysfunction. The number of patients with normal LV configuration increased within 6 months after the onset of therapy from 11.7 to 26.6% (p < 0.05). However, the difference was insignificant by the end of the study. The number of patients in group 1 with eccentric hypertrophy increased from 64.7 to 75.0% after 12 months (p < 0.05) but that with concentric hypertrophy decreased The data obtained suggest the necessity of early beginning of spironolactone therapy of CCF hearing in mind its positive effect on diastolic dysfunction.