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Section 8. Medical science
Section 8. Medical science
Kamilova Umida Kabirovna, PhD, ScD, The Republican Specialized Scientific Practical Medical Center of Therapy and Medical Rehabilitation,
Tashkent, Uzbekistan Abdullaeva Charos Abdudjalilovna, Tashkent Medical Academy, Republic of Uzbekistan E-mail: [email protected]
Features Glu298Asp polymorphizm GENE NOS-3 in patients with chronic heart failure of uzbek nationality
Abstract: Investigated the genetic determinants of the development of endothelial dysfunction — alleles and genotypes Glu298Asp NOS-3 gene in patients with CHF of Uzbek nationality.
Keywords: endothelial dysfunction, chronic heart failure, gene polymorphizm.
According to numerous studies, it became obvious that the effect of environmental factors is realized in connection with the genotype of the individual features. The problem is that not previously manifested in other living conditions of the particular genotype in the changed social conditions “implemented” its potential pathogenetic significance, become individual genetic risk factors, so the study of genetics of cardiovascular disease becomes more theoretical and practical significance [1; 2]. Identification of genetic risk factors for cardiovascular disease and to assess their contribution to the development of disease — one of the main problems of molecular cardiology. Genetic risk factors, as opposed to a clinical, biochemical, environmental and others. Risk factors are not modifiable (not subjected to correction) [3; 4]. Testing of susceptibility genes allows, first of all, to form a group of persons of high cardiovascular risk for the purpose of therapeutic and preventive measures aimed at reducing the extent of the risk under the supervision of a physician. Identification of the genetic predisposition to any disease can be carried out well before the onset of clinical symptoms, which can effectively prevent its development or postpone deadlines demonstrations [5]. However, molecular genetic testing can detect features of etiopathogenesis and course the most common cardiovascular disease in each patient.
It has long been proven that in the development of cardiovascular disease in general and heart failure, in particular, occupies a special place endothelial dysfunction [6; 7]. It has been suggested that endothelial dysfunction may be a primary, genetically determined. One of the genes, whose role in the development of endothelial dysfunction has been widely discussed in recent years, is the gene of endothelial NO-synthase (eNOS). The gene of endothelial NO-synthase (eNOS), responsible for the synthesis of nitric oxide (NO) and endothelium is a key enzyme in the regulation of vascular
tone, smooth muscles in the vascular wall and thrombotic processes. The gene encoding eNOS, located on chromosome 7q35-36, consists of 26 exons and encodes a protein with a mol. weight of 135 kDa, consisting of 1203 amino acids [3; 8]. ENOS gene promoter contains multiple domains, i. e. can be adjusted near the transcription factors [9].
It is the most studied polymorphism 4a/b 4th intron polymorphism G894T (Glu298Asp) 7th exon polymorphism and T-786S promotora gene eNOS. The exons and introns eNOS gene are the most important three polymorphic sites. This minisatellite repeat in intron 4 (4a/b polymorphism eNOS) and transversion G/T at position 894 of the nucleotide sequence of the gene eNOS, which leads to a mutation at position 298 of the protein sequence, leading to the substitution of glutamic acid for aspartic (Glu-Asp298) and polymorphism T-786S promotora gene eNOS [10; 11].
Genotype prevailing in one population may be minor to another, which makes the research for each ethnic and population groups with unique and meaningful [5; 7]. Genetic factors undoubtedly play an important role in the pathogenesis of heart failure, however, information about the clinical relevance of polymorphisms of genes in CHF is clearly not enough. The existing data or very vague or contradictory. According to reports, the frequency of polymorphisms of individual genes associated with the disease. However, the degree of evidence of this view in a number of cases is being questioned. Given the above it is of interest to study the features ofpolymorphism Glu298Asp NOS-3 gene in patients with CHF.
Material and methods. In patients with CHF 114 Uzbeks have been studied the genetic determinants of the development of endothelial dysfunction — alleles and genotypes Glu298Asp NOS-3 gene. The control group consisted of 75 healthy individuals — men of Uzbek nationality. Groups
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Features Glu298Asp polymorphizm GENE NOS-3 in patients with chronic heart failure of uzbek nationality
of age were sopostovimy. The study was performed according to the standards of Good Clinical Practice (Good Clinical Practice) and the Declaration of Helsinki. The study protocol was approved by the ethics committees of all participating clinical centers. Before inclusion in the study all participants provided written informed consent. All patients were divided into three groups of functional class (FC) of CHF according to the New York Heart Classification (NYHA) according to the test of 6-minute walk (TSHH): the first group consisted of 19 patients with CHF FC I, the second group 44 patients with FC II and 3 group — 51 patients with FC III classification NYHA. Study polymorphism Glu298Asp (894 G> T) gene of endothelial nitric oxide (eNOS) was conducted using polymerase chain reaction on programmable thermocycler CG-1-96 «Corbett Research» (Australia) and 2720 «Applied Biosystems» (USA), using kits LLC “Medlab” (St. Petersburg), according to the manufacturer’s instructions. In our work allele polymorphism G/T894 revealed after digestion of the amplified fragment of 206 bp containing the polymorphic site.
Oligonucleotide primers used for PCR f5-CATGAGGCTCAGCCCC-3’ r5’- AGTCAATCCCTTTGGTGCTC-3’
Evaluation of deviation of the distribution of genotypes of studied polymorphisms of DNA from the canonical distribution of Hardy-Weinberg equilibrium was performed using the computer program for the analysis of genetic data “GenePop” (“Genetics of Population"). To calculate the “odds ratio” (OR — odds ratio) with 95% confidence intervals (CI — confidence interval), ^2 and p values used statistical package statistical software package «OpenEpi 2009, Version 2.3».
Results and discussion
Analysis of the distribution of genotypes Glu298Asp NOS-3 gene in patients with CHF showed: Glu/Glu — I in patients with CHF FC was 84.2% in patients with FC II — 70.4%, and FC III — 64.7% (Table 1). Glu/Asp genotype 3 patients met FC I — 15.3%, in 12 patients with FC II and -27.3% in 17 patients with FC III CHF -33.7%. In the group of healthy individuals Glu/Glu genotype occurred in 92%, Glu/Asp at 6.7%.
Patients in the control group allele Glu was — 95.3%, and Alel Asp — 4,7%. Patients frequency vstechaemosti Glu — allele was distributed as follows: 92.1% in patients with CHF FC I, 84.1% in patients with class II and 81.4% in patients with FC III CHF.
Table 1. - The distribution of allele and genotype frequencies polimorfizma- Glu298Asp NOS-3 gene
№ Surveyed group The frequency of alleles The frequency of genotypes Total surveyed (n)
Glu Asp Glu/Glu norm (n) Glu/Asp Heterozygote (n) Asp/Asp Mutation (n
1 CHF FCI 92.1 7.9 84.2 (16) 15.8 (3) - 19
2 CHF FC II 84.1 15.9 70.4 (31) 27.3 (12) 2.3 (1) 44
3 CHF FC III 81.4 18.6 64.7 (33) 33.3 (17) 2.0 (1) 51
4 Total 84.2 15.8 70.2 (80) 62.7 (32) 1.75 (2) 114
5 Control 95.3 4.7 92.0 (69) 6.7 (5) 1.3 (1) 75
The analysis of population frequency in the control group showed that the frequency of allele distribution of RCE in the control group: Glu = 0.95; Asp = 0.05. The expected frequency distribution ofgenotypes ofRCE in the control group: Glu/Glu = 0.908; Glu/Asp = 0.089; Asp/Asp = 0.02. The observed frequency distribution of genotypes of RCE in the control group: Glu/Glu = 0.92; Glu/Asp = 0.067; Asp/Asp = 0.013. (X2 = 4.7; P = 0.03 (between expected and observed.).
In patients with heart failure frequency distribution of alleles in patients RCE: Glu = 0.84; Asp = 0.16. The expected frequency distribution of genotypes in patients RCE: Glu/Glu = 0.71; Glu/Asp = 0.27; Asp/Asp = 0.02. The observed frequency distribution of genotypes in patients RCE: Glu/Glu = 0.70; Glu/Asp = 0.28; Asp/Asp =
0.02 (X2 = 0.3; P = 0.5 (between expected and observed.).
Table 2. - The difference between the expected and observed frequencies of heterozygosity Glu298Asp
Groups Observed heterozygosity Expected heterozygosity D *
CHF 0.28 0.27 -0.04
CHF FCI 0.16 0.145 -0.1
CHF FC II 0.27 0.27 0
CHF FC III 0.33 0.3 -0.1
Control group 0.67 0.89 +0.33
In patients with CHF FC I allele frequency distribution of RH in patients: Glu = 0.9; Asp = 0.08. The expected frequency distribution of genotypes in patients RCE: Glu/Glu = 0.85; Glu/Asp = 0.145; Asp/Asp = 0.0062. The observed frequency distribution of genotypes in patients RCE: Glu/Glu = 0.84; Glu/Asp = 0.16; Asp/Asp = 0.00
(X2 = 0.1; P = 0.7 (between expected and observed.). In patients with class II alleles frequency distribution of RCE in patients: Glu = 0.84; Asp = 0.16. The expected frequency distribution of genotypes in a group of RCE Patients: Glu/Glu = 0.71; Glu/Asp = 0.27; Asp/Asp = 0.025. The observed frequency distribution of genotypes in patients
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Section 8. Medical science
RCE: Glu/Glu = 0.71; Glu/Asp = 0.27; Asp/Asp = 0.02 (X2 = 0.01; P = 0.9 (between expected and observed.). The frequency of allele distribution of RCE in patients with FC III CHF: Glu = 0.81; Asp = 0.19. The expected frequency distribution of genotypes in patients RCE: Glu/Glu = 0.66; Glu/Asp = 0.30; Asp/Asp = 0.035. The observed frequency distribution of genotypes in patients RCE: Glu/Glu =
0.65; Glu/Asp = 0.33; Asp/Asp = 0.02. (X2 = 0.5; P = 0.5 (between expected and observed)).
Relative deviation from the expected heterozygosity observed (D) polimorfizma- Glu298Asp NOS-3 gene was calculated using the formula: D = (hobs-hexp)/hexp, where hobs and hexp — expected and observed heterozygosity, respectively. Conclusion. Thus, the study of the distribution of alleles and genotypes Glu298Asp NOS-3 gene in patients with heart failure showed that progressirovinie CHF depends on the polymorphism of this gene and gene Glu298Asp NOS-3 is effective prognostic markers.
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Abdullaeva Charos Abdudjalilovna, Tashkent Medical Academy, Republic of Uzbekistan E-mail: [email protected]
Evaluation of the effect of omega-3 PUFA on lipid profile in patients with postinfarction cardiosclerosis complicated by congestive heart failure
Abstract: The effect of omega-3 PUFA on lipid profile in patients with postinfarction cardiosclerosis complicated by heart failure.
Key words: chronic heart failure, omega-3 PUFA, hypercholesterolemia.
The most common cause of heart failure (congestive heart failure) is coronary heart disease (CHD), which is 54-68,6%. About 50% ofpatients with CHF, despite the use of combination therapy, died within 5 years after the onset of clinical symptoms. The problem of the treatment of coronary heart disease (CHD) complicated with chronic heart failure (CHF) remains relevant,
as it has great social and economic importance. Today the main cause of morbidity, disability and mortality worldwide are cardiovascular disease. The prevalence of chronic heart failure (CHF) in the general population is 1.5-2%, and in persons over 65 years amounts to 10%. Forecasts are also disappointing: the researchers suggest that the prevalence of heart failure in
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