The Protective Effect of Polymorphisms rs2681472 and rs17249754 of the ATP2B1 Gene Against Coronary Artery Disease and Hypertension is Abolished by Tobacco Smoking.

Aim    To study the relationship of single nucleotide polymorphisms rs2681472 and rs17249754 in the ATP2B1 gene with risk of ischemic heart disease (IHD) and arterial hypertension (AH) among residents of Central Russia and to evaluate the trigger role of smoking as a risk factor for development of IHD and AH in carriers of ATP2B1 gene polymorphic variants.Material and methods    The study included DNA samples from 1960 residents of Central Russia of Slavic origin. Among them, there were 1261 patients with cardiovascular diseases and 699 healthy persons. The vast majority of patients had both IHD and AH. Genotyping was performed using the iPLEX technique on a MassARRAY-4 genomic mass-spectrometer. The relationship of ATP2B1 alleles, genotypes, and haplotypes with the risk of diseases was calculated by logistic regression analysis with adjustments for sex and age.Results    Carriage of AG and GG (rs2681472) genotypes and GA (rs17249754) genotype was associated with a reduced risk of both IHD (p=0.0057 and p=0.022 for rs2681472 and rs17249754, respectively) and AH (p=0.016 and p=0.036, respectively). Rare rs2681472G-rs17249754G and rs2681472A-rs17249754A haplotypes were associated with a reduced risk of IHD (odds ratio, OR, 0.22; 95 % CI: 0.11-0.46, p=0.0001) and AH (OR, 0.22; 95 % CI: 0.10-0.47, p=0.0001). Analysis of the groups stratified by the smoking status showed that in smokers, the studied polymorphic variants did not have a protective action with respect of either IHD or AH. However, in non-smokers, the genotypes AG and GG rs2681472 (OR, 0.62; 95 % CI: 0.47-0.80, p=0.0004) and GA rs17249754 (OR, 0.61; 95 % CI: 0.47-0.81, p=0.0004) were associated with a reduced risk of IHD and AH (OR, 0.63; 95 % CI: 0.48-0.83, p=0.0004 for rs2681472; OR, 0.63; 95 % CI: 0.48-0.83, p=0.001 for rs17249754), as well as the carriage of the minor alleles rs2681472­G and rs17249754­A.Conclusion    It was shown for the first time that the polymorphic variants rs17249754 and rs2681472 of the ATP2B1 gene are associated with a reduced risk for IHD and AH only in non-smokers.

[ESTIMATING THE EFFECTIVENESS OF HYPOLIPIDEMIC THERAPY WITH ROSUVASTATIN IN PATIENTS WITH CORONARY HEART DISEASE DEPENDING ON THE GENOTYPE OF LIPOPROTEIN LIPASE].

Taking into account the genetic heterogeneity of hyperlipidemias, polymorphic genes involved in the regulation of lipid metabolism may explain differences in the efficacy of hypolipidemic therapy. In the present prospective and randomized study, we have investigated the efficacy of rosuvastatin (10 mg/day) in the therapy of atherogenic hyperlipidemias in a group of 62 patients with coronary heart disease (CHD), depending on the genotype of lipoprotein lipase (LPL). The pharmacological correction was carried out during one year under control of lipid metabolism parameters (total cholesterol, LDL-C, HDL-C, HDL-unrelated cholesterol, triglycerides, atherogenic index) at the baseline and on 4th, 8th, 24th and 48th week. The HindIII polymorphism (+495T > G, rs320) of the LPL gene was genotyped in all patients studied through a real-time PCR TaqMan assay. Rosuvastatin produced a significant hypolipidemic effect with respect to all investigated lipid metabolism parameters for 24 weeks of treatment. Changes in the parameters of lipid metabolism upon rosuvastatin treatment differed in patients with genotype +495GG as compared to the rest LPL genotypes. In comparison to the +495TT and TG genotypes, the genotype +495GG showed a greater reduction in total cholesterol on 8th week, and in LDL-C, HDL-unrelated cholesterol, and atherogenic index on the 48th week of rosuvastatin therapy (p <0.01). It can be suggested that the pronounced hypolipidemic effect of rosuvastatin in homozygotes +495GG of the LPL gene is associated with modulation of the LPL activity, as it has been previously reported for other statin drugs.

[Genetic and biochemical mechanisms of involvement of antioxidant defense enzymes in the development of bronchial asthma].

In the present review we have analyzed and summarized recent literature data on genetic and biochemical mechanisms responsible for involvement of antioxidant defense enzymes in the etiology and pathogenesis of bronchial asthma. It has been shown that the mechanisms of asthma development are linked with genetically determined abnormalities in the functioning of antioxidant defense enzymes. These alterations are accompanied by a systemic imbalance between oxidative and anti-oxidative reactions with the shift of the redox state toward increased free radical production and oxidative stress, a key element in the pathogenesis of bronchial asthma.

Joint effect of glutathione S-transferase genotypes and cigarette smoking on idiopathic male infertility.

Inconsistent results of association studies investigated the role of glutathione S-transferase genes in idiopathic male infertility may be explained by ethnical differences in gene-gene and gene-environment interactions. In this study, we investigated a joint contribution of GSTM1, GSTT1 and GSTP1 gene polymorphisms and cigarette smoking to the risk of idiopathic infertility in Russian men. DNA samples from 203 infertile and 227 fertile men were genotyped by a multiplex polymerase chain reaction (GSTM1 and GSTT1 deletions) and PCR-restriction fragment length polymorphism (GSTP1 I105V) methods. The GSTP1 genotype 105IV was associated with increased risk of male infertility (OR = 1.50 95% CI 1.02-2.20 P = 0.04). Genotype combinations GSTP1 105II/GSTT1 del (G1), GSTM1 del/GSTT1 del (G2) and GSTM1 + /GSTT1 del (G3) were associated with decreased risk of male infertility (P ≤ 0.003), whereas a genotype combination GSTP1 105IV/GSTT1 + (G4) was associated with increased disease risk (P = 0.001). The genotype combinations G3 and G4 showed a significant association with infertility in smokers; however, nonsmokers carriers did show the disease risk. In conclusion, GSTM1, GSTT1 and GSTP1 genes are collectively involved in the development of idiopathic male infertility and their phenotypic effects on the disease risk are potentiated by cigarette smoking.

[The association study of the promoter polymorphism -308G>A of tumor necrosis factor gene with the development and severity of acute pancreatitis in Russian population of Kursk region].

The aim of this study was to investigate the relationship between the polymorphism -308G>A of tumor necrosis factor (TNF) gene and the risk and severity of acute pancreatitis (AP) in unrelated Russians from Kursk region. DNA samples were obtained from 190 AP patients and 217 healthy controls for genotyping the polymorphism through a TaqMan allelic discrimination assay. Although -308G>A genotypes did not show a significant association with disease risk, the genotype -308GA was found to be associated only with non-severe type of acute alcohol-related pancreatitis (odds ratio 1.81 (95% CI 1.02-3.23 p=0.04).

CYP2E1 gene promoter polymorphism -1293G>C increases the risk of essential hypertension in men with alcohol abuse.

We studied the association between of cytochrome P450 2E1 (CYP2E1) gene polymorphism and risk of essential hypertension development depending on alcohol drinking habit in unrelated men in Russian population (patients with essential hypertension and healthy volunteers). All participants were genotyped for four CYP2E1 gene polymorphisms -1293G>C (rs3813867), -1053C>T (rs2031920), 7632T>A (rs6413432), and 9896C>G (rs2070676) by PCR and restriction analysis. We found statistically significant associations between -1293C allele (OR=5.04, 95% CI=1.23-20.70, p=0.03) and -1293GC genotype (OR=5.36, 95% CI=1.28-22.50, p=0.03) with increased risk of essential hypertension in men. Stratified analysis on alcohol drinking habit showed that the presence of -1293C allele (OR=6.82, 95% CI=1.12-41.70, p=0.04) and -1293GC genotype (OR=7.61, 95% CI=1.2-48.4, p=0.03) in men with alcohol abuse increases the risk of essential hypertension. The obtained data suggest that excessive alcohol consumption and increased induction of cytochrome in the carriers of -1293C allele of CYP2E1 gene lead to generation of highly reactive free radical oxidation products. These processes induced oxidative stress and endothelial induction, which served as the pathogenetic basis for essential hypertension.

[Polymorphism Gly460Trp of alpha-adducin gene and predisposition to essential hypertension. The role of gene-environment interactions in the development of the disease in Russian population].

In this study we for the first time in Russian population elucidated association between G460W polymorphism of -adducin gene (ADD1) and risk of development of hypertensive disease (HD). DNA samples from 205 patients with HD and 207 healthy nonrelated individuals of Russian nationality were genotyped for G460W polymorphism of ADD1 gene by polymerase chain reaction and restriction analysis. We detected no statistically significant differences between groups of healthy people and patients with HD. But among smokers with 460GW genotype of ADD1 gene we found elevated risk of HD development (OR 2.71, 95%CI 1.01-7.26; p=0.04). Among nonsmokers the given genotype did not influence risk of origination of the disease (OR 0.67, 95%CI 0.39-1.15; p=0.15). Moreover carriers of 460GW genotype who did not consume fresh vegetables and fruits or consumed them insufficiently (once a day or less) had the highest risk of HD development (OR 2.24, 95%CI 1.06-4.73; p=0.03) while in subjects who consumed fresh vegetables and fruits regularly the given genotype possessed protective properties in relation to risk of development of the disease (OR 0.25, 95%CI 0.09-0.68; p=0.005). Thus in the studied Russian population G460W polymorphism of ADD1 gene can be considered as predisposition gene to HD, but its pathological effect is manifested solely under influence of environmental factors.

[A protective effect of GLY272SER polymorphism of GNB3 gene in development of essential hypertension and its relations with environmental hypertension risk factors].

AIM: To study associations of C825T (rs5443) and G272S (rs16932941) polymorphisms of GNB3 gene in Russian population of the Central Chernozem region with essential hypertension (EH) risk; to elicit the role of environmental risk factors in realization of EH predisposition in this gene genotypes carriers. MATERIAL AND METHODS: We studied DNA samples obtained from 205 EH patients and 207 healthy individuals. EH patients were treated in Kursk hospitals. Genotyping of GNB3 gene polymorphisms was conducted by polymerase chain reaction and restriction analysis. RESULTS: Prevalence of 82ST allele of GNB3 gene in EH patients and healthy individual was 0.334 and 0.295, respectively, of 272S allele--0.037 and 0.058, respectively. We found no significant differences by prevalence of genotypes of gene GNB3 polymorphisms C825T and G272S in EH patients and healthy individuals. Non-smoking carriers of 272GS genotype had a low risk of EH (OR 0.42 in 95% CI from 0.18 to 0.97; p = 0.04). Smokers had no protective effect of this genotype. The protective effect of 272GS genotype was also found in individuals with low or moderate alcohol drinking habits (OR 0.29 in 95% CI from 0.11 to 0.77, p = 0.02) and in individuals without chronic exposure to stress (OR 0.29 in 95% CI from 0.09 to 0.91, p = 0.04). In contrast, hard drinkers and patients exposed to chronic stress had no protective effect of heterozygous genotype 272GS of gene GNB3. CONCLUSION: G272S polymorphism of GNB3 gene can be considered as a new genetic marker of predisposition to EH. The protective effect depends of environmental factors associated with high risk to develop EH.

[Influence of three point mutations in TNF-alpha promoter gene in clinical manifestations and complications of stomach and duodenal ulcer].

The purpose of our study was to investigate whether polymorphisms -238G/A, -308G/A, and -863C/A within the promoter of the TNF-alpha gene are associated with clinical features of gastric and duodenal ulcer disease in a Russian population. DNA samples of 381 unrelated patients with gastric and duodenal ulcer disease and 216 sex- and age-matched healthy controls were used to determine the TNF-alpha gene polymorphisms by PCR-RFLP assay. Logistic regression analysis has revealed significant associations of polymorphism -308G/A with size of ulcerous defect (p=0.03) and intestinal dyspepsia (p=0.05), polymorphism -238G/A with gastric dyspepsia (p=0.04) and reflux-esophagitis (p=0.05), polymorphism -863C/A with perforation of ulcer (p=0.04). The study results highlight impact of the TNF-alpha gene polymorphisms on various clinical features in patients with peptic ulcer disease.

Genetic variation of myeloperoxidase gene contributes to atopic asthma susceptibility: a preliminary association study in Russian population.

BACKGROUND: Recently, we have shown that both antioxidant and oxidant genes are proper candidates for asthma susceptibility genes. OBJECTIVES: In the present study we investigated whether a common polymorphism -463G > A in the promoter of myeloperoxidase (MPO) gene, an enzyme producing hypohalogenic oxidants, is associated with the risk of bronchial asthma. METHODS: We studied 429 unrelated Russian subjects including 215 asthmatic patients and 214 sex- and age-matched healthy controls from Central Russia. The genotyping of the polymorphism -463G > A in the MPO gene was performed by the polymerase chain reaction and the restriction fragment length polymorphism assays. RESULTS: It was found that a carriage of a -463A allele is associated with decreased risk of asthma (OR 0.64 95%CI 0.44-0.91, p = 0.013). Furthermore, variant genotypes (-463GA + AA) of the MPO gene were associated with decreased risk of asthma (OR adjusted by age, gender, and immunoglobulin E (IgE) level was 0.63 95%CI 0.42-0.95), but at a borderline statistical significance (Bonferroni corrected p = 0.017). Further analysis revealed that both a -463A allele and the -463GA/AA genotypes are significantly associated with decreased risk of atopic asthma (p = 0.01). No association of the -463G > A polymorphism of the MPO gene with non-atopic asthma has been revealed. We also found that the allele -463A (OR = 0.47 95%CI 0.27-0.81, p = 0.01) and the -463GA + AA genotypes (OR 0.43 95%CI 0.24-0.78, p = 0.005) are significantly associated with decreased risk of late-onset atopic asthma (the disease onset after 30 years). No association of both allele and genotypes of the polymorphism -463G > A of the MPO gene with early-onset of atopic and non-atopic asthma (the disease before 30 years) was seen. CONCLUSIONS: The results of this study provide novel insights into pathogenesis of bronchial asthma. We put forward a suggestion about a possible mechanism by which the -463G > A polymorphism of the MPO gene is involved into pathogenesis of asthma.

[Polymorphism -930A > G of the cytochrome b gene is a novel genetic marker of predisposition to bronchial asthma].

AIM: To evaluate the link between promotional polymorphism -930A > G of the cytochrome b gene (CYBA) and onset of bronchial asthma; to examine effects of this locus on the risk of the disease development depending on the pro- and antioxidant action of environmental factors. MATERIAL AND METHODS: We studied samples of DNA obtained from 214 healthy individuals and 215 patients with bronchial asthma treated in Regional Kursk Hospital. We used polymerase chain reaction and analysed polymorphism of restriction fragments lengths for genotyping of -930A > G polymorphism of CYBA gene. RESULTS: Incidence of a variant allele -930G of CYBA gene among men with nonallergic bronchial asthma (nBA) was higher than in healthy men (OR 1.95; CI 1.02-3.73; p = 0.04). The homozygous variant genotype -930G/G was associated with a high risk of nBA in males (OR 2.66; CI 1.14-6.20; p = 0.02). In healthy individuals polymorphisms -930A > G and 640A > G were in negative linkage equilibrium (D = -0.057; p < 0.001) while in patients such associations were not registered. Male smokers with genotype -930G/G had the highest risk of nBA (OR 2.86; CI 1.06-7.77; p = 0.04) while non-smokers with this genotype had no risk of the disease (OR 1.50; CI 0.11-19.64; p = 0.70). Males with -930G/G on low or no vegetable diet had the highest risk of nBA (OR 3.11; CI 1.01-9.63; p = 0.04) while regular vegetable eaters had no risk to develop nBA (OR 0.73; CI 0.30-1.82; p = 0.50). CONCLUSION: We were the first to find relations between -930A > G polymorphism of CYBA gene and predisposition to nBA. This association exists in males and depends on the smoking status and vegetable diet.

Tobacco smoking, fruit and vegetable intake modify association between -21A>T polymorphism of catalase gene and risk of bronchial asthma.

Although oxidative stress is a cardinal feature of bronchial asthma, the role of interactions between environmental oxidant/antioxidant exposures and antioxidant genes in asthma aetiology has yet to be determined. The present study was conducted to investigate whether two common polymorphisms -21A > T and -262C > T of catalase (CAT) gene are associated with susceptibility to asthma in a Russian population and to test the hypothesis that the asthma risk attributed to CAT genotypes could be dependent on both oxidant (tobacco smoking) and antioxidant (fruit and vegetable intake) exposures. A total of 429 unrelated Russian individuals from Central Russia were recruited in the study, including 215 asthmatics and 214 sex- and age-matched healthy controls. Genotyping analysis for the CAT gene polymorphisms was performed by PCR-RFLP assays. The frequencies of both allele -21A (OR 0.73 95%CI 0.55-0.96 p = 0.03) and -21AA CAT genotype (OR 0.42 95%CI 0.23-0.76 p = 0.004) were higher among asthmatics than among healthy controls. The frequency of -21AA genotype of the CAT gene was significantly higher in patients with allergic (OR 0.47 95%CI 0.25-0.92 p = 0.024) and nonallergic (OR 0.32 95%CI 0.14-0.71 p = 0.004) asthma in comparison with controls (at the Bonferroni corrected p value less than 0.025). Polymorphisms -21A > T and -262C > T of the catalase gene were in a positive linkage disequilibrium (p < 0.0001). Smokers who carried -21AA genotype had an increased risk of nonallergic asthma (p = 0.002), whereas nonsmoker carriers of this genotype did not have the risk of any variant of the disease. Notably, no association of CAT genotype -21AA with asthma was found in high fruit and vegetable consumers, whereas low fruit and vegetable consumers (one time per day or less often) possessing this genotype were at increased risk of both allergic (p = 0.013) and nonallergic (p = 0.008) asthma. This is the first study reporting an association of polymorphism -21A > T of the catalase gene with allergic and nonallergic asthma. We also found, for the first time, that cigarette smoking and fruit and vegetable intakes have potentially inverse modifying influences on the asthma risk in individuals with -21AA CAT genotype and that the gene-environment interactions that were found support the biologic plausibility of catalase gene for the development of bronchial asthma.

[Association of C242T and A640G polymorphisms in the gene for p22phox subunit of NADPH oxidase with the risk of bronchial asthma: a pilot study].

Genetic control of free radical oxidation, generation of reactive oxygen species, as well as of preoxidant and antioxidant balance in airway diseases, including bronchial asthma, is an important issue of the research in pulmonology. The present study is the first investigation of association between two common polymorphisms, C242T (exon 4) and A640G (3' untranslated region), within the NADPH oxidase gene (CYBA) and the risk of bronchial asthma. Samples of asthma patients (n =209) and healthy controls (n = 210) of Russian nationality were examined. Genotyping of the CYBA C242T and A640G polymorphisms was performed using polymerase chain reaction and restriction fragment length polymorphism. It was demonstrated that the frequency of heterozygous CYBA genotype A640G in bronchial asthma patient group was lower than that in control group (OR = 0.66; 95%CI, 0.45-0.97; P = 0.04). Separate analysis of different clinical pathogenetic variants of the disease showed that homozygous wild-type CYBA genotype A640A was associated with the increased risk of allergic bronchial asthma (OR = 1.76; 95%CI, 1.07-2.90; P = 0.03), while heterozygous CYBA genotype A640G was associated with the decreased risk of this form of the disease (OR = 0.63; 95%CI, 0.41-0.96; P = 0.03). Thus, a new candidate gene for allergic bronchial asthma was discovered. Possible mechanisms of the involvement of CYBA in the development of asthmatic phenotype are discussed.

The relationship between polymorphisms in the glutamate cysteine ligase gene and asthma susceptibility.

The present study was designed to investigate an association of common -588C/T and -23G/T polymorphisms within glutamate cysteine ligase modifier subunit gene with susceptibility to bronchial asthma. A total of 435 ethnically Russian subjects were recruited in this study, including 221 patients with asthma and 214 sex and age matched healthy subjects. As previously reported, the -588C/T and -23G/T polymorphisms were completely linked. The -588TT/-23TT genotype was found to be associated with decreased risk of allergic asthma after adjustment for age, gender and smoking status using multivariate logistic regression analysis (OR=0.33 95% CI 0.15-0.70, p=0.036). However, the -588CT/-23GT genotype was associated with increased risk of non-allergic asthma (OR=2.03 95% CI 1.05-3.90, p=0.06). This is a first study reporting the association between genetic variations in the glutamate cysteine ligase gene and susceptibility to bronchial asthma.

[Heterozygosity of 198LEU mutant allele in glutathione peroxidase-1 gene as a risk factor of bronchial asthma associated with smoking].

AIM: To investigate whether smoking has a differential effect by Pro198Leu genotypes of the glutathione peroxidase-1 (GPx1) gene on the risk of bronchial asthma (BA) in Russian population. MATERIAL AND METHODS: DNA samples from 195 asthmatics and 167 healthy volunteers were genotyped for Pro198Leu polymorphism of the GPx1 gene by polymerase chain reaction and restriction fragment length analysis. RESULTS: Smoking was significantly associated with an increased risk of non-allergic BA in males but not in females (p < 0.00001). When smoking was examined according to Prol98Leu polymorphism of the GPx1 gene, association of 198Pro/Leu genotype with susceptibility to allergic BA was found only in male smokers (odds ratio = 2.51, 95% confidence interval = 1.04 to 6.06, p = 0.04). CONCLUSION: The risk of allergic BA associated with smoking is increased in males who are heterozygous carriers for the low-activity 198Leu allele of the glutathione peroxidase-1 gene. The importance of molecular mechanisms is shown by which functional variants of antioxidant defense genes may mediate potentially oxidative effects of tobacco smoke on asthmatic phenotype.

Arg25Pro polymorphism of transforming growth factor-beta1 and its role in the pathogenesis of essential hypertension in Russian population of the Central Chernozem Region.

We studied the relationship between Arg25Pro polymorphism of TGFbeta1 gene and predisposition to essential hypertension in the Russian population of Central Chernozem Region (n=402). An association was found between 25Pro allele and 25ArgPro genotype with low risk of essential hypertension in male individuals.

[Polymorphism of Y-chromosomal microsatellites in Russian populations from the northern and southern Russia as exemplified by the populations of Kursk and Arkhangel'sk Oblast].

Allelic polymorphisms at five Y-chromosomal microsatellite loci (DYS19, DYS390, DYS391, DYS392, and DYS393) were typed in 87 individuals from male population samples from two geographically isolated regions (Arkhangelsk oblast and Kursk oblast) of the European part of Russia. The populations examined demonstrated substantial differences in the distribution of the DYS392 (P = 0.005) and DYS393 (P = 0.003) alleles. Estimates of genetic relationships between these populations and some other European populations (including Eastern-Slavic) showed that irrespectively of the measure of genetic distance chosen, Arkhangelsk population was closer to the populations belonging to the Finno-Ugric linguistic group (Saami and Estonians) and to the Estonian geographical neighbors, Latvians, while Kursk population was the member of a cluster formed by Eastern-Slavic populations (Russians of Novgorod oblast, Ukrainians, and Belarussians). Phylogenetic analysis of the most frequent haplotypes indicated that these differences between Kursk and Arkhangelsk populations were associated with high prevalence in the latter of major haplotypes characteristic primarily of the Finno-Ugric populations.

The contribution of genetic and environmental factors to quantitative variability of erythrocyte membrane proteins in primary hypotension.

Our previous studies have shown that, compared with healthy individuals, patients with primary arterial hypotension (PAH) have significant quantitative changes in erythrocyte membrane proteins. The purpose of the present study was to evaluate the contribution made by genetic and environmental factors to quantitative variation of erythrocyte membrane proteins in PAH. We studied 109 hypotensive patients, 124 normotensive subjects, 222 of their first-degree relatives and 24 twin pairs by sodium dodecyl sulphate (SDS) polyacrylamide gel electrophoresis. The decomposition of total phenotypic variance of erythrocyte membrane proteins to genetic and environmental components was performed on the basis of correlations among first-degree relatives by the least squares method. The genetic dominance and shared environmental factors were found to influence the variability of cytoskeletal membrane proteins whose contents were changed in PAH. Furthermore, variations in alpha-spectrin, actin and anion exchanger in hypotensives were substantially influenced by major gene and maternal effects. Ankyrin 2.1 and actin content was under the control of common underlying genes. Variations in membrane-associated glutathione-S-transferase and tropomyosin were predominantly affected by polygenes. These findings suggest that the putative major genes with pleiotropic effects appear to be involved in the control of quantitative disorders of erythrocyte membrane proteins in primary hypotension.

[Contents of the main erythrocyte membrane proteins in patients with primary arterial hypertension and its relationship with hereditary predisposition to cardiovascular diseases]. / Soderzhanie osnovnykh belkov membran éritrotsitov u bol'nykh pervichnoi arterial'noi gipotoniei i ego sviaz' s nasledstvennoi predraspolozhennost'iu k serdechno-sosudistoi patologii.

AIM: To study quantitative content of main erythrocyte membrane proteins in patients with primary arterial hypotension and its relationship with hereditary predisposition to cardiovascular disease. MATERIAL AND METHODS: Quantitative content of main erythrocyte membrane proteins in 109 patients with primary arterial hypotension (PAH) and 124 healthy persons was measured with unidimensional polyacrylamide gel electrophoresis. Hereditary determination of PAH was studied by the clinical-genealogical method. RESULTS: PAH patients showed quantitative alterations in erythrocyte membrane protein composition: increased content of alpha-spectrin, ankyrin (band 2.1), anion exchange protein (band 3) and decreased content of actin, tropomyosin and glutathione-S-transferase. Patients with aggravated heredity for PAH had higher content of beta-spectrin and ankyrin (band 2.1 and 2.2) then patients without aggravated heredity for PAH. CONCLUSION: Quantitative alterations of membrane proteins in patients with PAH could significantly modify the structure of cytoskeleton and result in modification of the enzyme activity of transmembrane proteins (ATPases) regulating cation transport across erythrocyte membrane. Moreover, aggravated heredity for PAH predisposes to high content of cytoskeletal proteins (beta-spectrin, 2.1 and 2.2 ankyrin) which could form more compact structure of erythrocyte membrane and limit cation influx into cytoplasma.