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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, p perm =0.03). Four haplotypes of MMPs have a protective effect on the development of stroke with hypertension (OR=0.48-0.50, p perm =0.02-0.03). Four models of gene-gene interactions of polymorphic MMPs loci (OR=2.19-2.55, p perm <0.001) and three four-factor models of gene-environment interactions of MMPs with alcohol abuse (OR=2.82-3.11, p perm <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.

Glaucoma is one of the most common eye diseases leading to blindness, and whole-genome studies have shown that genetic factors are important in its formation., Purpose - to perform an in silico analysis of the functional significance of polymorphic loci of the LOXL1 gene associated with glaucoma, using data from wholegenome studies., Material and Methods: Using the catalog of genome-wide studies (GWAS) of the National Human Genome Research Institute (https://www.genome.gov/gwastudies/), three polymorphic loci of the LOXL1 gene (rs2165241, rs4886776, rs893818) associated with glaucoma (pseudoexfoliation glaucoma/syndrome) were chosen for the study. Using modern databases on functional genomics (SIFT, PolyPhen-2, HaploReg, GTExportal), the functional significance of these polymorphic loci was assessed (nonsynonymous substitutions, epigenetic effects, association with gene expression, associations with alternative splicing of gene transcripts)., Results: The work establishes the important functional significance of the rs2165241, rs4886776 and rs893818 polymorphic loci of the LOXL1 gene. They demonstrate significant epigenetic effects (affect the affinity to five transcription factors, are located in the region of promoters and enhancers, in the region of hypersensitivity to DNase-1), are associated with the expression and alternative splicing of three genes ( LOXL1 , LOXL1-AS1 , RP11-24D15.1 ) in cell cultures, organs and tissues pathogenetically significant for development of glaucoma, are strongly linked to the rs1048661 polymorphism, which causes the replacement of the Arg141Leu amino acid in the LOXL1 polypeptide., Conclusion: Polymorphic loci of the LOXL1 gene (rs2165241, rs4886776, and rs893818) are of great functional importance (epigenetic, eQTL, and sQTL), which may be the biomedical basis of their associations with glaucoma.

Primary open-angle glaucoma (POAG) is the most common form of glaucoma in which genetic factors play a significant role. According to genome-wide studies (GWAS), the CDKN2B-AS1 gene is associated with POAG., Purpose: To study in silico the functional significance of the CDKN2B-AS1 gene polymorphism GWAS-significant for primary open-angle glaucoma., Material and Methods: The in-silico analysis was based on data from the GWAS catalog, five polymorphic loci of the CDKN2B-AS1 gene (rs1063192, rs7865618, rs2157719, rs944800, rs4977756) associated with POAG were selected. The study evaluated the regulatory potential, the relationship with the expression and alternative splicing of genes of the CDKN2B-AS1 gene polymorphism using modern databases for functional genomics - HaploReg and GTExportal., Results: An important functional significance of the polymorphic loci rs1063192, rs7865618, rs2157719, rs944800, rs4977756 of the CDKN2B-AS1 gene was revealed. These loci are located in the region of histones marking enhancers and in the region of hypersensitivity to DNAse-1, can be found in more than ten different organs and tissues, in the regions of regulatory DNA motifs to five transcription factors (AIRE, GATA, Tgif1, Pou2f2, and Zfp187), and are associated with expression of three genes ( CDKN2B-AS1, CDKN2B, CDKN2A ) and alternative splicing of transcripts of two genes ( CDKN2B-AS1 and RP11-149I2.4 ) in cell cultures, organs and tissues with pathogenic significance for glaucoma development., Conclusion: Polymorphism of the CDKN2B-AS1 gene (rs1063192, rs7865618, rs2157719, rs944800, rs4977756) has significant regulatory potential and is associated with the expression and alternative splicing of genes, which possibly underlies its association with primary open-angle glaucoma.

The article reviews literature on the role of matrix metalloproteinases (MMP) in the development of eye pathologies, specifically primary open-angle glaucoma (POAG). Regulation of the extracellular matrix is carried out by proteolytic enzymes - metalloproteinases in particular - as well as specific inhibitors of their activity (tissue metalloproteinases inhibitors). The review also reveals its involvement in the pathogenesis of various types of glaucoma, decrease in stability of the intraocular liquid outflow, proves the role of MMR in the ganglionic apoptosis, remodeling of the optic disk and change of lamina cribrosa in primary open-angle glaucoma. There is research devoted to studying the interrelations of MMP genes with POAG development. Associations of single nucleotide polymorphic loci of MMP-1, MMP-2, MMP-9 genes with POAG are shown.

The article reviews literature covering the etiopathogenesis and risk factors for the development of primary open-angle glaucoma (POAG). Currently, this problem is one of the most complex and controversial in ophthalmology. The review considers the main theories: vascular, mechanical (retentional, hydromechanical), dystrophic (theory of primary scleropathy), metabolic, concept of liquor hypertension, concept of the individual norm of intraocular pressure, as well as POAG risk factors.

The article reviews literature on developmental stages of genome-wide association studies (GWAS) of primary open-angle glaucoma (POAG). This problem is currently developing and one of the most complex in ophthalmology. The article considers main GWAS of POAG and established GWAS-significant polymorphisms associated with the disease. The topic of genome-wide studies of primary open-angle glaucoma will be of certain interest to ophthalmologists, materials on GWAS-significant loci can be used both in the selection of polymorphisms in replicative studies of POAG in various populations of Russia, and to expand ideas about the molecular genetic mechanisms of the development of the disease.

The aim of research. To study the association of polymorphic loci of matrix metalloproteinases with the development of essential hypertension (EH) in men of the Central Chernozem Region of Russia. Materials and methods. A study of 564 men with EH and 257 control men was performed. Analysis of the polymorphic loci of metalloproteinases rs11568818 MMР7, rs1320632 MMР8, rs11225395 MMР8, rs1799750 MMР1, rs3025058 MMР3 was performed using real-time PCR. The study of associations of SNPs and their haplotypes with the development of arterial hypertension was carried out using logistic regression analysis in the PLINK software (v. 2.050). The regulatory potential of polymorphic loci was analyzed in the HaploReg software (v. 4.1) (http://archive.broadinstitute.org). The effect of SNP on gene expression was studied using the data of the Genotype-Tissue Expression project (http://www.gtexportal.org/). Results. Haplotype including rs11568818 MMP7, rs1320632 MMP8, rs11225395 MMP8 and rs1799750 MMP1 associated with a high risk of disease in men (OR=2,58, pperm=0,04). These polymorphisms located in region of promoter and enhancer histone marks and in the region of hypersensitivity to DNAse-1. They located in sites of proteins bound (TBP, CJUN, CFOS and GATA2) and they associated with the level of gene expression ММР7, ММР27 and RP11-817J15.3 (in peripheral blood, skeletal muscles, nervous tissue and other). Сonclusion. Haplotype G-A-C-1G for polymorphisms rs11568818 MMP7, rs1320632 MMP8, rs11225395 MMP8, rs1799750 MMP1 are associated with the development of essential hypertension in men in the Central Chernozem Region of Russia.

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.

Primary open-angle glaucoma (POAG) is a multifactorial disease, etiopathogenesis of which largely depends on growth factors. Possessing a variety of medical and biological effects, these cytokines may influence the development and progression of POAG., Aim: to reveal the role of genetic polymorphisms of growth factors in predisposition to developing POAG that is refractory to local hypotensive therapy., Material and Methods: The object of the study were 162 patients with stage II-III POAG, in whom local hypotensive therapy was inefficient, 90 patients with stage II-III POAG well controlled on local hypotensive therapy, and 191 controls. The material for the study was venous blood taken from the cubital vein of a proband. Isolation of genomic DNA was performed by phenol-chloroform extraction. Analysis of genetic polymorphisms of growth factors was performed through allelic discrimination. For that, synthesis of DNA was carried out via polymerase chain reaction (PCR)., Results: It is found that the T IGFR-1 genetic variant (OR=1.34) and a combination of the C VEGF-A and T IGFR-1 genetic variants (OR=1.90) are risk factors of developing POAG that is refractory to local hypotensive therapy. A statistical model for predicting such a risk has been proposed that includes: VEGF-A с.-958C>T genetic marker (rs 833,061), age, concomitant non-inflammatory ocular diseases, microvascular changes in the conjunctiva, the degree of pigmentation of the angle of the anterior chamber, and pseudoexfoliative syndrome. Recognition accuracy of the model is 90.42%., Conclusion: The T IGFR-1 genetic variant and a combination of the C VEGF-A and T IGFR-1 genetic variants increase the risk of developing POAG that is refractory to local hypotensive therapy.

Aim: To investigate whether the functionally relevant -844G>A promotor polymorphism in the catalase (CAT) gene is associated with the development of essential hypertension (EH)., Subjects and Methods: The investigation enrolled 2,339 unrelated ethnic Russian people, including 1,269 EH patients and 770 apparently healthy individuals. Genotyping of CAT -844G>A (rs769214) polymorphism was performed using a TaqMan real-time polymerase chain reaction assay., Results: The -844A allele (odds ratio (OR)=1.31; 95% confidence interval (CI), 1.04 to 1.64; р=0.02) and the -844AA genotype (OR=1.41; 95% CI, 1.02 to 1.94; р=0.03) were found to be related to a higher risk of EH in the smokers. No association was found between this polymorphism and EH risk in the non-smokers., Conclusion: Smoking is a predisposing factor for development of EH in CAT -844AA genotype carriers.

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.

We investigated the association of polymorphisms of genes tumor necrosis factors and their receptors (-308G/A TNFa, +250A/G Lta, +36 A/G TNFR1, +1663 A/G TNFR2) with the predisposition to the development of essential hypertension (EH) and the features of its clinical course in patients with metabolic syndrome. It has been demonstrated that the molecular genetic marker +36G TNFR1 (OR=1,25) is involved in the formation EH in individuals with metabolic syndrome. The risk of stage III EH in patients with metabolic syndrome is enhanced by genetic variants -308GA TNFa (OR=2,72), -308A TNFa (OR=2,72), +250G Lta (OR=1,80), and combinations thereof -308A TNFa with +1663G TNFR2 (OR=3,85), +250G Lta with +36G TNFR1 (OR=3,85), +250G Lta with +1663G TNFR2 (OR=3,85) while protective properties are inherent in -308GG TNFa (OR=0,32), +250AA Lta (OR=0,45), -308G TNFa (OR=0,37), +250A Lta (OR=0,56) and a combination of genetic markers -308GG TNFa with +250A Lta (OR=0,31), -308G TNFa with +250AA Lta (OR=0,39), -308G TNFa with +250A Lta (OR=0,31).

The study analyzed 301 patients with uterine cancer at the age of 45 years and older and 304 patients with uterine myoma 45 years. It was found that patients with uterine myoma of the older age group (45 and older) have the following clinical features: overweight and thus increased BMI these women, a lower percentage of a family history of uterine cancer, a smaller percentage of infertility, a greater number of pregnancies, births, medical abortions, the high prevalence of diseases of the cardiovascular system and pathology of the cervix, large size fibroids and as a consequence more common compartment syndrome adjacent organs by myoma nodes (disuric disorders).

The aim was to study bioinformatics involvement of candidate genes of cytokines in the formation of large fibroids in women with uterine cancer in older age groups. Genotyping of 15 molecular genetic markers cytokines was performed in 120 patients with uterine myoma with large myoma nodes and 107 patients with myoma nodes of small size. The study found that genetic risk factors for fibroids with large uterine fibroids are two combinations of genetic variants: G SDF-1, CC IL-1β, A RANTES (OR=5,56) and A RANTES with genotype CC IL-1β (OR=4,60). 12 of 15 polymorphic loci studied in various combinations (8 revealed significant combinations) have protective value in the formation of large fibroids with uterine cancer (OR=0,09-0,31).

The results of the study of Y-chromosomal polymorphisms of Russian and Ukrainian population are presented for Slobozhanshina--contemporary border region, former "Wild Field" boundary, which was inhabited in XVII-XVIII centuries by both the Russians from the north and Ukrainians from the west. In general, Ukrainian and Russian populations of Slobozhanshchina genetically are very close, their set and frequency range of Y-chromosome haplogroups are typical for the Eastern Europe. But a detailed analysis of highly informative Y-chromosome markers showed that after 3,5 centuries of coexistence on the same historical territory, the both nations retain the ethnic specificity of their gene pools: Ukrainian populations are similar to the rest of Ukraine, and Russian populations are similar to the south of the European part of Russia. The genetic differences may be due to the spatial characteristics of marriage migration and the predominant ethnic environment.

The present review is devoted to genetic studies of primary open-angle glaucoma (POAG). Today, POAG is considered a multifactorial disease with threshold effect, which is associated with single or multiple genes mutation as well as external influences. According to molecular genetic studies, three causative genes (MYOC, optinevrin, WDR 36) and several dosens of candidate genes are involved in the development of POAG.

We conducted the first genetic analysis of a wide a range of rural Russian populations in European Russia with a panel of common DNA markers commonly used in criminalistics genetic identification. We examined a total of 647 samples from indigenous ethnic Russian populations in Arkhangelsk, Belgorod, Voronezh, Kursk, Rostov, Ryazan, and Orel regions. We employed a multiplex genotyping kit, COrDIS Plus, to genotype Short Tandem Repeat (STR) loci, which included the genetic marker panel officially recommended for DNA identification in the Russian Federation, the United States, and the European Union. In the course of our study, we created a database of allelic frequencies, examined the distribution of alleles and genotypes in seven rural Russian populations, and defined the genetic relationships between these populations. We found that, although multidimensional analysis indicated a difference between the Northern gene pool and the rest of the Russian European populations, a pairwise comparison using 19 STR markers among all populations did not reveal significant differences. This is in concordance with previous studies, which examined up to 12 STR markers of urban Russian populations. Therefore, the database of allelic frequencies created in this study can be applied for forensic examinations and DNA identification among the ethnic Russian population over European Russia. We also noted a decrease in the levels of heterozygosity in the northern Russian population compared to ethnic populations in southern and central Russia, which is consistent with trends identified previously using classical gene markers and analysis of mitochondrial DNA.

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).

In the course of the performed study the significant influence of pesticides introduced into arable farmland, on the frequency of gynecological morbidity in adolescents in 21 districts of the Belgorod region was established. With increasing pesticide load on the soil the prevalence of gynecological pathology in adolescents in rural areas is raising.

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).

Yu. P. Altukhov suggested that heterozygosity is an indicator of the state of the gene pool. The idea and a linked concept of genetic ecological monitoring were applied to a new dataset on mtDNA variation in East European ethnic groups. Haplotype diversity (an analog of the average heterozygosity) was shown to gradually decrease northwards. Since a similar trend is known for population density, interlinked changes were assumed for a set of parameters, which were ordered to form a causative chain: latitude increases, land productivity decreases, population density decreases, effective population size decreases, isolation of subpopulations increases, genetic drift increases, and mtDNA haplotype diversity decreases. An increase in genetic drift increases the random inbreeding rate and, consequently, the genetic load. This was confirmed by a significant correlation observed between the incidence of autosomal recessive hereditary diseases and mtDNA haplotype diversity. Based on the findings, mtDNA was assumed to provide an informative genetic system for genetic ecological monitoring; e.g., analyzing the ecology-driven changes in the gene pool.

The study of the influence of geliophysical factors on neonatal morbidity in the Belgorod Region in 2000 to 2008 established a rise in the rate of congenital malformations, fetal hypoxia and asphyxia, prematurity, and overall neonatal morbidity during a period of high solar activity.

Data on the frequencies of all (50 412) surnames in a total population of 849 399 people have been treated by various methods of multivariate statistics (cluster analysis, multidimensional scaling, and factor analysis) to show that 22 district populations of the Central Chernozem region of Russia form a definite, ordered system of population groups. All raions (administrative districts) of Belgorod oblast (administrative region) have been grouped into four clusters corresponding to the actual geographic locations of the populations. Districts of the eastern cluster are characterized by very specific spectrum and frequencies of surnames; districts of the western cluster differ in a high proportion of Ukrainian surnames.

The model of the Belgorod oblast population has been used to demonstrate different effects of administrative reforms on microevolution in human populations. For the populations that formerly belonged to Kursk oblast, changes in the regional administrative structure (after which some of them remained in Kursk oblast and others were included into Belgorod oblast) have lead to an increase in the genetic distances between them. However, other populations (formerly belonging to Voronezh oblast) have become genetically closer to one another, although these populations now belong to different administrative regions (Belgorod and Voronezh oblasts).

The investigation revealed statistically significant positive and negative correlations between the impact of solar activity (SA) and the incidence of congenital malformations (CM). As SA decreased, the incidence of multiple CM, defects of the musculoskeletal system, and those as a whole increased, but among the nosological entities, there was a rise in the prevalence of diaphragmatic hernia and omphalocele. At the same time, increased SA determines the higher incidence of abnormalities of the central nervous system, sensory organs, face and neck, anencephalies, and cleft lips. The maximum influence of SA was established for CM of the skin (56.25%), face and neck (53.46%); and among the nosological entities of CM that was for the cleft lip (60.65%) and cerebrospinal hernia (46.51%).

Changes in the endogamy indices of district populations of the Central Chernozem region of Russia during the past 100 years were studied. The size of an elementary population in this region increased from that of a rural municipality in the mid-20th century to that of an administrative district in the late 20th century.

The frequencies of 33 alleles of 12 loci of immunological and biochemical gene markers (ABO, RH, HP, GC, TF, PI, C'3, ACP1, GLO1, PGM1, ESD, and 6-PGD) have been estimated in the indigenous Russian and Ukrainian populations of Belgorod oblast. Differences of the Belgorod population from other populations of Russia with respect to the genetic structure have been determined. It has been found that the frequency distributions of all alleles studied in the Belgorod population are similar to those typical of the genetic structure of Caucasoid populations.

The characteristics of the gene pools of indigenous populations of Ukraine and Belarus have been studied using 28 alleles of 10 loci of biochemical gene markers (HP, GC, TF, PI, C'3, ACP1, GLO1, PGM1, ESD, and 6-PGD). The gene pools of the Russian and Ukrainian indigenous populations of Belgorod oblast (Russia) and the indigenous populations of Ukraine and Belarus have been compared. Cluster analysis, multidimensional scaling, and factor analysis of the obtained data have been used to determine the position of the Belgorod population gene pool in the Eastern Slavic gene pool system.

S u m mary. The paper presents the results of studying the qualitative and quantitative representation of anthropogenic pollutants in the ambient air environment of Belgorod and evaluating their impact on the prevalence of neonatal congenital malformations. The level of atmospheric pollutant emissions is shown to vary by an average of 4 to 10 times in some areas. The vast majority (91.7%) of pollutants form clusters (n = 11), suggesting their combined influence. Each group of clusters includes 2 to 9 pollutants (median 4.64 pollutants). Atmospheric pollutants have been ascertained to adversely affect the prevalence of congenital malformations in children. A multiple regression equation has been derived to predict the frequency of congenital malformations, by taking into account the qualitative and quantitative spectrum of atmospheric pollutants.

Diseases of respiratory organs constitute a serious socio-medical problem in this country due to high morbidity, mortality, and disability rates. The development of medical nanotechnlogies opens up new prospects for the improvement of treatment and prevention of these pathologies. Of special interest is application of C60fullerenes with a broad spectrum of therapeutic activities and synthesis of their hydrated forms for enteral and parenteral administration producing no acute or chronic toxic effects.

The frequencies and spectra of surnames have been analyzed in groups of raions (districts) of the Belgorod oblast (region) with different degrees of population subdivision. The "family name portraits" of districts with low (0.00003 less sign f* < 0.00022, f*(r) = 0.00015) and moderate (0.00023 < f*(r) < 0.00042, f*(r) = 0.00029) inbreeding levels are similar both to each other and to the "family name portrait" of the Belgorod oblast as a whole. Districts with high subdivision levels (0.00043 < f*(r) < 0.00125, f*(r) = 0.00072) had very distinctive surname spectra and the highest surname frequencies. Intense immigration to the Belgorod oblast significantly affects its population genetic structure, decreasing the population subdivision.

The gene pool of the entire population of all the 21 raions (districts) of the Belgorod oblast (region) has been studied using anthroponymic data. Considerable geographic variations of the number of surnames and the degree of population subdivision (0.00003 < f(r)* < 0.00125) in the 21 districts have been demonstrated. Districts with low population subdivision levels are mainly located in the central and southwestern raions of the Belgorod oblast, contain an urbanized area (city), and border on Ukraine (they are characterized by a considerable Ukrainian immigration). Urbanization significantly affects the population structure of the Belgorod oblast. In urbanized districts, rural populations lack the relationships between the population size, number of surnames, and population subdivision level (f(r)).

The aim of the study was to investigate genetic characteristics of patients with chronic obstructive bronchitis (COB) using classic biochemical markers, their contribution to the development and course of the disease, and morphological peculiarities of erythrocytes in these patients. The subjects were 60 COB patients and 50 practically healthy people; their serum samples were studied. The following classic biochemical markers were investigated: haptoglobin; transferrin; C3 compliment component; group-specific component; ABO blood systems and Rh-factor. Erythrocytometry of blood smears was performed upon admission and before discharge. The study evaluated the contribution of heredity to the forming of COB and established specific genetic markers of predisposition to the development of COB and certain features of its clinical course; the condition of peripheral blood erythrocytes in COB patients was studied.

Based on the characteristics of body height and weight in 4905 newborns, the population-genetic structure of the rural raions (districts) of Kursk oblast (region) and in the city of Kursk was determined. An "adaptive norm area" with respect to body weight and height was distinguished for newborns in Kursk oblast. On the average, the anthropometric parameters of 20% of infants from the studied populations fell within this area. The height and growth of newborns exhibited a pronounced geographic variation and depended on the level of urbanization, as well as the sex and the health status of the newborns. In district populations, the body height and the variances of the body height and weight increased with an increase in endogamy. Therefore, the relative numbers of newborns with large values of both weight and height, as well as those with a medium body height and a small body weight, were increased. Conversely, the relative numbers of newborns with a low weight and height and with a disturbed weight-height correlation were decreased.

The distributions of AB0 and Rhesus phenotypes and the corresponding genes in the population of Kursk oblast were studied. Based on these data, genetic differentiation of rural populations with respect to the d gene frequency was revealed. The differentiation was determined by the differences in the genetic and demographic structure of these rural populations. The frequency of homozygotes for the recessive gene d and the incidence of malformations affecting the children's viability increased with an increase in the inbreeding level of a population. Genetic distances between the population of Kursk oblast and other populations were estimated.

A significant effect of the population structure on the incidence of multifactorial diseases affecting the viability of the adult population was found in rural districts of Kursk oblast. The diseases studied were chronic bronchitis, pulmonary emphysema, pneumosclerosis, and atherosclerosis. The incidence of multifactorial pathology increased with an increase in the homozygosity level of district populations. On average, the population structure affected the incidence of multifactorial diseases by 30-50%.

The coefficient of inbreeding and its components were calculated for populations of rural districts of Kursk oblast with the use of the isonymic method. The following values were obtained: F(it) = 0.000567, Fst = 0.000650, and Fis = 0.000083. The Fst value agreed with the value of Malecot's local inbreeding coefficient (0.000201). In the districts where the proportions of families with frequent family names (FFNs; a frequency of 0.001 and more) were 50% and over, these family names were sufficient to adequately describe the population structure. The migration index and the index of family-name diversity were calculated. Significant correlations were revealed between Fst, the migration index, the index of family-name diversity, Malecot's local inbreeding, the mean square distance between birthplaces of spouses, the effective migration pressure, and the coefficient of linear systematic pressure.

Investigation of the the genetics, demography, and epidemiology of congenital malformations (CMs) in Kursk oblast revealed statistically significant correlations between population parameters and the incidence of CM in the rural rations of the oblast. The general prevalence of CM and that of the separate CM forms ("guard" CM, multiple CM, hemangioma, congenital heart disease, congenital myelocele, talipes valgus, congenital femoral luxation, polydactyly, cryptorchism) increased with an increase in the average marital age of men and women of the reproductive part of the population and with an increase in the level of the populations homozygosity (an increase in the local consanguinity and ethnic marriage assortativeness, a decrease in the populations's migration activity, an increase in the proportion of genotypes homozygous for recessive genes, etc).

Total selection indices and their components in the Kursk Oblast, calculated from Crow's equations, are: Itot = = 0.403, I(f) = 0.345, Im = 0.043. The selection intensity was higher in rural than in urban populations. The levels of total selection and differential fertility in rural populations depended on the genetic and demographic structure of these populations. An increase of homozygosity in the rural populations (decreases in the mean square distance between spouses' birthplaces and in the frequency of long-range migrations, increase in ethnic assortativeness, etc.) increased the selection intensity.

Strong associations between demographic parameters characterizing age, ethnic composition, and migrational processes in the population have been revealed by means of multivariate methods (correlation and cluster analyses; the method of principal components). Formation of the demographic structure of a population has been shown to be related to these associations, their directions and strength. In the long term, these associations determine features of subdivision (territorial, hierarchic, etc.) of the demographic structure of a particular population.

When studying the marriage structure of the Kurskaya oblast population in 1987-1990, a positive marriage assortativeness with respect to ethnicity was found (K = 0.244). The Russian population exhibited panmixia; in the Ukrainian population, negative marriage assortativeness and panmixia prevailed; other ethnic groups were characterized by more or less pronounced positive marriage assortativeness. The ethnic compositions of raion (district) populations were determined by their geographic location and history. The parameter of marriage assortativeness with respect to age was r = 0.911; this value in the reproductive part of the population was r = 0.748. The age of contracting marriage in the raion populations depended on the extent of their urbanization.

The distribution of and time trends in congenital defects of development (CD) influencing viability of children in the Kursk region were studied on the basis of 4517 autopsy reports for the period 1985-1994. A total of 880 children had CD (5.40%). The incidence of CD in towns (6.38%), was higher than in country regions (4.91%), p < 0.001, being the highest in the central parts of the region. Among the stillborns the specific proportion of congenital defects was 14.53%, perinatal deaths occurred in 16.96%, deaths during the 1st year of life in 22.10%. The percentage of multiple congenital defects, the defects of cardiovascular system, developmental anomalies of digestive system, the defects of central nervous system and organs of sense was 39.77, 27.16, 10.11 and 8.30, respectively.

The population of the Kurskaya oblast (administrative region) was described using the Malecot's model of isolation by distance. Differences in inbreeding level between populations of raions (districts) were found; the differences were determined by degrees of urbanization, age, and effective size of the populations. In the center of the oblast, an area was found with the minimum mean square distance between birthplaces of spouses, low effective migration pressure, and high isolation by distance. In populations of raions, a relationship was found between population inbreeding level and incidences of congenital malformations (CM) and multiple congenital malformations (MCM), which affected the viability of infants.

Analysis of marital structure revealed that 82% of men and 77% of women that contracted marriages in the Kurskaya oblast (administrative region) in 1987-1990 were born in this region. The average coefficient of demographic migration in the Kurskaya oblast was m = 0.345. The majority of migrants to the Kurskaya oblast were from neighboring areas: Central and Central Chernozem Zones of Russia, Ukraine, and Moldova. Marriage assortativeness with respect to the birthplaces of the spouses was K = 0.090. Migration activity increased with urbanization of the population. Migration structure of local populations was determined by mode, level, and direction of interaction between the processes underlying it.

Analyzes the effects of urbanization on the demographic structure of population. An increase in the degree of urbanization was found to be paralleled by an increase of the age qualification and of the migration activity of the population. The national composition of the population does not depend on urbanization.

Age characteristics, national composition, migration processes, and the level of inbreeding among Kursk citizens were analyzed on the basis of a sampling study of marriages registered in Kursk in 1960 and 1989. Assortative marriages in reference to age were r = 0.910 in 1960 and r = 0.904 in 1989. The polychoric relationship index characterizing national correlation of married pairs was K = 0.440 in 1960 and K = 0.405 in 1989. Positive assortive mating in reference to the birthplace of the married pairs was revealed: K = 0.190 in 1960; K = 0.161 in 1989. The coefficient of local population relationship (a) was 0.000026 in 1960 and 0.000011 in 1989.