Search

The concentration of total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) were determined among students of PFUR aged 17-25, from different climatic and geographical regions. In all the concentrations (> 6.2 mmol/L) of total plasma cholesterol were detected at 6 (2.4%) students, indicating a high or very high risk of coronary heart disease (CHD). Elevated levels of plasma LDL-C (> 3.31 mmol/l) were found at 4 (1.6%) students, indicating a high or very high risk of coronary heart disease. Lower concentrations of HDL-C plasma (< 1.31 > 1.1 mmol/L) were detected at 30 (12.4%) indicating a moderate risk of CHD and at 11 (4.6%) students concentration of HDL-C were lower (1,1 mmol/L), indicating a high risk of coronary heart disease. The results can be used as a justification for the screening survey to identify dyslipidemia among adolescents and young adults, with the subsequent conducting of the individual preventive and therapeutic measures.

Variability of cholesterol levels inside lymphocytes (CLL) have been compared with the concentration of total cholesterol, triglycerides and HDL of blood plasma among normal donors and hyperlipidemic patients. Persons with elevated CLL was found among normal donors and hyperlipidemic patients, each group comprising 4-5%. No significant correlation was followed between CLLthe level of total cholesterol, triglycerideHDL blood plasma level among total observed population. However a consistent correlation was found between CLLblood plasma cholesterol/triglyceride ratio among patient with elevated plasma triglyceride.

A genetic and epidemiological sample of 20-59-year-old males, Moscow residents (n = 3141), was surveyed. The authors obtained data on the prevalence of coronary heart disease from epidemiological criteria and genealogical data on cardiovascular diseases by the "Familial History" questionnaire in the first-degree relatives who were interviewed by using a genetic and mathematical monolocus diallelic model. It was found that out of the 10 possible variants under study a genetic and environmental variant with independent penetrance of 3 genotypes adequately describes the prevalence of coronary heart disease in the families and in the population. This suggest that both genetic and environmental factors have an influence on the prevalence of coronary heart disease and that there is a possible genetic polymorphism of the disease.

The rate of endogenous cholesterol synthesis in blood lymphocytes and skin fibroblasts from patients with type IIa hyperlipidemia was found to be increased in comparison with healthy donors. The cells of hyperlipidemic patients had lowered levels of glucocorticoid receptors concomitantly with a partial loss of their sensitivity to glucocorticoids. In fibroblasts from patients with hereditary hypercholesteremia of homozygous type the number of glucocorticoid receptors did not exceed 10% of their content in normal cells. The decrease of the number of glucocorticoid receptors in patients with type IIa hyperlipidemia seems to be a compensatory response of cells culminating in activation of endogenous cholesterol synthesis.

The paper gives the results of survey of 99 families of patients with prior myocardial infarction. There was a high coronary heart disease (CHD) affliction among the blood relatives of probands and its clear-cut relationship to the specific features of their family history. The patients with prior myocardial infarction and their blood relatives showed profound changes in coagulative and anticoagulative factors, which indicate their tendency to hypercoagulation. The specific features of family history, the pattern of changes in hemostatic parameters in blood and non-blood relatives, and evidence for the genetic determination of the hemostatic parameter activity suggest that the blood coagulative system is an important component for hereditary predisposition to CHD. An association of some hemostatic parameters was examined with CHD. The paper provides strong evidence for the fact that it is expedient to measure antithrombin III activity as a marker of genetic predisposition to CHD while surveying a group of individuals who have a family history of CHD.

Contribution of genetic and environmental factors in phenotypic variability of blood pressure level and skinfold thickness, and phenotypic correlation between these characters was calculated on the basis of familial correlations. It was shown that genetic determinant explains considerable portion of blood pressure level and skinfold thickness variability. Among common environmental effects, the factors affecting one generation are important with regard to variability of these characters. Maternal effect is expressed in the variability of systolic and diastolic blood pressure. Correlation between blood pressure level and triceps skinfold thickness is determined by genetic factors, whereas that between blood pressure level and subscapular skinfold thickness is mediated by environmental factors. The results obtained may be applied in populational prevention of cardiovascular disease.

Cardiovascular diseases give rise to high morbidity, mortality and infirmity, inflicting heavy social losses on a population (Chazov and Klimov 1980; Oganov 1990). Ischaemic heart disease (IHD) and high blood pressure (HBP) represent a major contribution (Chasov et al. 1986; WHO 1985, 1986).

The hypolipidemic agent bezamidine, a fibroic acid derivative (KPKA, Yugoslavia), was applied to treat Types 2a, 2b, 4 and 5 familial hyperlipoproteinemias. The highest reduction in plasma cholesterol and triglyceride concentrations was found in patients with Types 2b, 4 and 5 familial hyperlipoproteinemias. No clear-cut adverse effects of the drug were found during 3 months.

Using the RELP analysis we studied the frequency of X2 allele of apoB gene in three groups of patients: 1) men at the age of 20-59 with lipid metabolism disorders revealed in population inspection of Oktyabrsky district in Moscow; 2) men with ischaemic heart disease and 3) healthy men. It was established that in individuals suffering from type IIa hyperlipidemia the frequency of X2 allele was significantly higher than in healthy donors from Moscow population. Homozygotes for X2 allele of XbaI RELP had 7-9% higher serum cholesterol levels, than homozygotes for X1 allele. The study suggests the X2 allele of the apoB gene to be associated with the development of high plasma cholesterol level. No significant difference in X2 allele frequencies was found between patients with ischaemic heart disease and healthy donors. There was also no association found between cholesterol and triglyceride levels and the presence of X2 allele in this group of patients.

Contribution of genetic and environmental factors into phenotypic variability of blood pressure and body mass as well as into phenotypic correlation between these traits was defined. It was shown that additive genetic determinant is responsible for considerable level of blood pressure and body mass variability. Those common environmental factors are of importance which operate within the limits of one generation. Maternal effect of systolic and diastolic blood pressure variability is negligible. The correlation between systolic and diastolic blood pressure is determined both by environmental and genetic factors, whereas that between blood pressure and body mass is mediated by only environmental factors. The contribution of environmental factors into correlation between blood pressure and body mass lessens with age. The results obtained may be applied in development of population and individual programmes for preventing cardiovascular diseases.

Based on intrafamilial correlations, a component genetic analysis was used to evaluate the contribution made by genetic and environmental factors to variance in body weight and skin fold thickness in children who had various blood pressure. In children with initially elevated and normal blood pressures, the phenotypic variation in the body weight and adipopexia is largely determined by genetic factors, whereas in those with initially lower blood pressure, the phenotypic variation in the above parameters is greatly affected by environmental factors, mainly by those of occasional nature. The findings provide evidence for a differential approach to the primary prevention of hyper- and hypotension in children and adolescents.

Blood lipid and lipoprotein concentrations were measured in proband children with different levels of arterial pressure and in their relatives in the populational familial study. Based on intrafamilial correlations the component analysis of the phenotypic dispersion of total cholesterol, high density lipoprotein cholesterol and triglyceride concentrations was performed. Qualitative and quantitative differences were shown to exist in genetic and environmental determinants of lipids and lipoproteins in the families of probands with low, high and normal levels of arterial pressure.

Fatty acid spectrum of blood plasma, erythrocyte, and thrombocyte membranes as well as its alterations after diet therapy, containing polyunsaturated/saturated fatty acids at the ratio of I and less than 350 mg of cholesterol per a day, was studied in patients with hereditary hypercholesterolemia using gas chromatography. Content of linoleic acid was increased and that of oleic and arachidonic acids--decreased in lipids of the patients blood plasma as compared with healthy persons; an increase of linoleic acid was also detected in thrombocyte lipids. Alterations in fatty acid spectrum of erythrocyte membranes were less pronounced. After the course of diet therapy within I month a further increase in content of linoleic acid was observed in blood plasma. Under these conditions efficiency of essential fatty acids incorporation into lipid structures of thrombocyte membranes was higher and of erythrocytes--lower in the patients as compared with healthy persons. Possible alimentary correction of fatty acid spectrum in blood lipids is discussed.

Examination of 166 families of the patients who had sustained myocardial infarction revealed aggregation of coronary heart disease in the families and the atherogenic shifts in the parameters of lipid turnover, which were caused by significant influences of genetic factors. The close relatives of the postinfarction patients were shown to display a large proportion of monogenic forms of hyperlipoproteinemias.

Results are reviewed of the studies concerning genetics of hypertension. Evidence is provided for its genetic determination of the disease and biochemical control of blood pressure by the renin-aldosterone-angiotensin system. Approaches to the therapy and prevention of hypertension are proposed on the basis of own clinical and population studies. The methods are discussed to study genetics of hypertension using genetic markers.

In a representative aboriginal male Chukchi population, relationships were examined between major lipid-protein components of high-density lipoproteins (HDLP) and their subclasses (HDLP2 and HDLP3) and physiological plasma testosterone patterns. A single-trend correlation was established between cholesterol and phospholipids of each of the HDLP subclasses, and plasma triglycerides and testosterone. Apo-AI for each of the HDLP subclasses showed different trends of correlation with both triglycerides and normal range of testosterone. The findings are indicative of different patterns in the formation of HDLP2 and HDLP3 particles.

A genetic analysis of the characteristics of sugar curve (138 pairs) and cholesterol levels (CS) in the plasma (283) was carried out on a twin sample of 18-40 years old, taken from the Twin Register. Estimation of heritability were 0.66 for the sugar level in the blood before taking breakfast (S0), 0.5 for the sugar level 1 hour after taking 50 g of glucose (S1); 0.43 for the sugar level 2 hours after taking glucose (S2), and 0.38 for CS. There were genetic correlations between all the four characteristics, and they were 0.7 for S0-S1; 0.12 for S1-S2; 0.6 for S0-S2. Genetic correlation between the characteristics of sugar curve and the CS levels were 0.28 for CS-S0; 0.38 for CS-S1; 0.26 for CS-S2.

The authors studied the content of total cholesterol (Ch), triglycerides (TG), CS of high density lipoprotein (HDL2 and HDL3) subclasses and testosterone in blood plasma of 30-59-year-old males, natives or newcomers of Chukotsk, and compared the results with the corresponding values determined in the male population of Moscow. It was established that the mean HDL Ch concentration in blood plasma was higher and the content of TG and to a lesser degree that of total CS, was lower in the Chukchi males than in the male Moscow population and in the newcomers who were examined. It was also shown that in hypo- and hyper-alphalipoproteinemia in all groups examined, the content of HDL2 Ch changed for the most part (decreased or increased, respectively) while the level of HDL3 Ch remained relatively stable.

Genetic markers Hp, Gc, EstD and phosphoglucomutase (PGM) were studied in patients with essential hypertension (EH). The authors proved relationship between GcI-I-genotype and predisposition to EH. Heterozygote type 1-2 of the Gc-system was more resistant to the disease. The authors conclude that genetics markers may make the basis for studying the EH etiology and determining its more etiologically similar forms.

The method of calculating the threshold levels of blood plasma cholesterol and triglycerids was analysed. The threshold levels were used for a genetic analysis of the relatives of the probands with coronary heart disease combined with hyperlipoproteinemia. Among 25 relatives of probands suffering coronary heart disease combined with hyperlipoproteinemia the latter was found in 15, while among 25 relatives of probands suffering coronary heart disease and having normal lipid levels hyperlipoproteinemia was found only in 2. The presented data characterise the peculiarities of the diagnosis of familial (primary) hyperlipoproteinemia and support the importance of the hereditary factor in the regulation of lipid metabolsm in the families of coronary atherosclerosis patients.

Genetic analysis of the structure of phenotypical correlatin between systolic and diastolic blood pressure (BP) was carried out on a twin sample (72MT, 122 - of the same sex and 79 - of different sexes DT at the age of 18-40) taken from the Twin Register of the Institute of Medical Genetics, Academy of Medical Sciences of the USSR. Because of heterogeneity of general dispersions of ABP characteristics in different twin subgroups, the method is suggested of a correction of coefficient values of interclass correlation which for the systolic ABP was rMT=0.558, rDT=0.252, and for the foastolic ABP was rMT=0.454, rDT=0.271. Estimations of heritability were 0.612 for systolic and 0.365 for diastolic ABP. There was observed a significant genetic correlation in ABP characteristics which made ra=0.76; the correlation conditioned by general environmental factors being re=0.69. Thus, 76% of genetic and 69 environmental factors, determining the levels of systolic and diastolic ABP were general. The significance was discussed of the obtained results in the light of physiological pharmacological and clinical data.

The correlative contribution of environmental and genetic factors in determining the levels of cholesterol (CS) of high density lipoproteins (HDLP) and their subfractions (HDLP2 and HDLP3) was studied on a twin model. The predominant role of the genetic component in the interindividual variability of CS HDLP3 both in females and in males and a relatively greater contribution of the environmental component in CS HDLP2 variability were revealed. This explains the greater lability of CS HDLP2 concentrations under different environmental effects.

It is shown that phenotypic correlation of atherogenic index (AI)-[(total cholesterol--HDL-cholesterol)/HDL-cholesterol] with liability to IHD equals to 0.47. Based on AI values, the discrimination of individuals into the groups with IHD and without it could be obtained with the error of 29%. Intrapair correlations in the groups of twins and offspring-parent are as follows: rmz = 0.669 (125 pairs), rdz = 0.342 (228 pairs), rop = 0.466 (65 pairs). Partition of AI total phenotypic variance based on correlations among relatives by the least square method allowed to obtain the following estimates: Ga = 68.5%, Ew = 31.5%. Based on the monogenic model, inheritance of "hyper-AI" phenotype (AI higher than the 90% threshold of normal distribution) corresponds to the quasidominant mode with the parameters: p = 12.8% (frequency of the "hyper-AI" allele), II2 = 78.8% (penetrance of homozygotes for the tested allele), II1 = 39.4% (penetrance of heterozygotes) provided that penetrance of opposite homozygotes II0 = 0.

Three groups of families with different initial levels of arterial pressure in proband children were examined. The relationship was established between the levels of arterial pressure in children and those in their relatives of the first degree of kinship. Based on intrafamilial correlations, the phenotypic dispersion of systolic and diastolic arterial pressure was analyzed. It has been shown that as compared to the genetic factors, the environmental factors play a greater role in arterial pressure variability.

Analysis of the results of a populational genealogical and epidemiological study into coronary heart diseases (CHD) carried out among the nonorganized male population aged 20-54 years living in Alma-Ata supports the importance of hereditary predisposition to the development of CHD as one of the leading risk factors for the illness. The rate of heart attacks (HA) in the diseases histories of the fathers and mothers of CHD persons was higher than among the parents of healthy persons. The mean values of cholesterol and triglyceride levels appeared much more significant in persons having both parents with a history of HA.

The structure of phenotypic and genetic correlations between ABO blood groups, MN, Rh(D), haptoglobins and concentration indications of the total cholesterol, of sugar curve, the levels of systolic and diastolic arterial pressure was studied in twins by the method for cluster analysis (121 monozygotic twin pairs, 120 dizygotic like sex twin pairs and 107 pairs of unlike sex twins). No correlation between the systems analysed and their indications on the phenotypic level was observed. By analysis of genetic correlations, the existence of correlations between the Rh system and arterial pressure, and the total cholesterol concentration, as well as between the ABO system and sugar concentration indexes, was established. Possible genetic causes for correlations obtained are being discussed.