The renin-angiotensin-aldosterone system (RAAS) is involved in the pathogenesis of Coronary Heart Disease and myocardial infarction. The crucial component of the RAAS is angiotensin II and its effects are carried out by angiotensin II receptors 1st type (AT1R). Aim of the study: determine the incidence of the mutant allele of the AT1R gene, estimate possible correlations between AT1R gene polymorphism and the extension of endothelial dysfunction in patients who have suffered MI in the age under 45. Materials and methods: 122 men suffering myocardial infarction under the age of 45 have been examined. In all patients we measured a relative increase of brachial artery diameter during the test with reactive hyperemia, the number of circulating endotheliocytes. Identification of A1166C polymorphism of the AT1R gene was carried out by means of polymerase chain reaction (PCR). Results: in patients with a history of myocardial infarction in the age under 45 we have found evidence of endothelial dysfunction: increased circulating endotheliocytes, decreased endothelium-mediated vasodilation. Among patients with a vasoconstrictive reaction the incidence of the C allele of the AT1R gene was higher than in patients exhibitng a vasodilative response during a test with reactive hyperemia (P<0.007). The incidence of the mutant allele of the AT1R gene was reliably lower in coronary patients with arterial hypertension than in those without hypertension.

At present the inherited defects in homeostasis are believed to play an important role in pathogenesis of venous thrombosis. In the current study the frequencies of the following polymorphisms: FVLeiden, G20210A FII, ΡΙ Α7ΡΓ 2 GPIIIa, G(-455)A FGB, C677T MTHFR and L/S SLC6A4 were estimated in the group of patients with venous thrombosis of different localization (193 persons included 41 pediatric patients) and in the control group (282 patients). The FV Leiden, A20210 FII, simultaneous carrying of T677 MTHFR and FVLeiden, simultaneous carrying of T677 MTHFR and LL SLC6A4 were appeared to be the risk factors of venous thrombosis development in young age.

One of the leading anticoagulants in Russia is warfarin. Its pharmacokinetics is determined by structural polymorphisms of CYP2C9 cytochrome gene, metabolizing warfarin. In the present study, the authors analyzed: 1) prevalence of two allele variants of this gene; 2) patients' individual reaction to warfarin, according to their CYP2C9 genotype. It was demonstrated that: 1) prevalence of CYP2C9 gene allele variants in St. Petersburg population was 82,66% (CYP2C9*1), 11,11% (CYP2C9*2), and 6,32% (CYP2C9*3); 2) individuals with CYP2C9*2 and CYP2C9*3 alleles reached therapeutic hypocoagulation faster, and required significantly lower weekly doses of the medication. Routine identification of CYP2C9*2 and CYP2C9*3 alleles is recommended to all patients administered warfarin.

Analysis of allele distribution of four single nucleotide polymorphisms (C-17G, C69T, G-191C and 319insG) of promoter and 5'-untranslated regions of the ABCA1 gene was carried out in a sample of 171 men, who had survived myocardial infarction before 45 years, and in controls. Two-fold increase of T69 and C-191 allele frequencies were observed in Russian population in comparison to Dutch one. While comparing allele and genotype distributions of the polymorphisms in the samples under study no statistically significant differences were found, so as no influence of different alleles on lipid spectrum data was observed. Role of polymorphisms under study appears to be insignificant in formation of genetic susceptibility to myocardial infarction in young men.

The incidence of allele variants of glutathione-S transferase M1 xenobiotic detoxification gene and matrix metalloproteinase 9 gene was analyzed in patients with chronic obstructive pulmonary disease. A strict gene-gene interaction between these two genes in the formation of hereditary predisposition to this disease was first demonstrated. The combination of glutathione-S transferase M1 genotype 0/0 and matrix metalloproteinase 9 mutant allele (-15621) is a risk factor for chronic obstructive pulmonary disease (OR-7.7).

Hypoacusis is a common sensory defect in humans which creates problems in communication. Heredity is essential in etiology of hypoacusis and deafness. Genes PAX3 and MITF were studied in patients with Vaardenburg syndrome in 14 unrelated families. Five mutation defects in the gene PAX3 were found. This provided the final diagnosis of the syndrome in these families.

The rate of D allele did not differ between patients with ischemic heart disease (IHD) who had myocardial infarction before the age 45, and healthy males. The DD genotype of the ACE gene was much more frequently encountered in the patients than in healthy males. The findings suggest that the DD genotype is an independent risk factor of the IHD and myocardial infarction in young patients.

Polymorphisms of 3 apolipoprotein genes Xba I apoB, Sstl apoCIII, and apoE and the insertion-deletion polymorphism of the angiotensin-converting enzyme gene (I/D ACE) and lipid levels were studied in a random sample of 403 children and adolescents aged 6 to 18 years living in St. Petersburg. The children were divided in 4 age groups with consideration for the relative body weight index: group 1.6 to 9 years; II, 10-12; III, 13-15; and IV, 16-18 years. The first three groups were divided by sex, the fourth was not because it was the smallest. Relationships between lipid levels and DNA polymorphisms of the above genes were analyzed in all groups. Effects of apoB Xbal, apoCIII Sstl, apoE, and ACE genotypes on the levels of the blood basic lipids were analyzed using Statgraphics software. A marked effect of the apoE (E3/E4) genotype on the total and LDL-cholesterol variability was observed in group IV. The individuals carrying the E4 apoE allele had increased levels of total and LDL-cholesterol (p < 0.02 and p < 0.03, respectively). The level of triglycerides was higher in the subjects carrying the S2 apoCIII allele in the third group (p < 0.04). A statistically reliable difference was however observed only in girls (p < 0.01). We failed to detect reliable correlations between lipid levels and various apoB and ACE genotypes. Hence, the genetic variants of apoCIII and apoE genes affect the blood lipid levels as early as in adolescence.

Specimens of DNA isolated from the cells of primary colorectal carcinomas (CRC) were examined for molecular-genetic alterations in a number of oncogenes and antioncogenes and for deletions of some chromosome 17 regions. Amplification of oncogene erbB-1 was found in 2 of 56 (4%) specimens, and amplification of erbB-2 in 4 of 62 (6%). No amplification of oncogene c-myc was revealed in any of 67 CRCs. Loss of heterozygosis (LH) of chromosome 11p (probe hras-1) was observed in 2 of 37 informative CRC specimens. Deletions of oncogene hras-1 alleles were not accompanied by point mutations in the ''hot'' codons (12th and 61st) of the remaining allele of this gene. Alleles A3 and A4 of the hras-1 oncogene were shown to be prevalent in CRC patients as compared with healthy donors. No gross structural alterations were found in antioncogenes rb-1 (41 cases) or p53 (62 cases). LH of chromosome 17p (probe ynz-22) occurred in 15 of 26 (58%) CRC cases and of 17q (probe thh-59) in 4 of 16 (25%). Among 35 CRC cases only one point mutation was detected in the 175th codon of gene p53. Complex Southern blot analysis of the above molecular-genetic abnormalities in 40 CRC cases revealed alterations in 23 cases (58%). No correlation could be established among any genetic alterations or with the clinical parameters of the tumors. The experimental data presented in this work contradict the widespread viewpoint about the obligatory involvement of the p53 suppressor gene in chromosome 17 deletions in CRC.

The methods for enzymatic DNA amplification in vitro that allow to avoid the step of preliminary DNA extraction and purification are proposed. Lysates of blood cells in the solution or immobilized on the nylon membrane filters and dried blood spots on the filter paper blotters were used directly in amplification permitting one to solve the problems of adapting the method of polymerase chain reaction in clinical practice, for instance, in massive screening of genome mutations, viral infections etc.

Upon amplification in vitro of the 12th exon area of the human phenylalanine hydroxylase gene followed by allele-specific hybridisation of the amplification product with synthetic probes and its sequencing by the Maxam-Gilbert method, a C----T transition causing phenylketonuria has been identified in Latvian patients.

A mutation causing beta 0-thalassaemia in Azerbaijanian population is shown, by the polymerase chain reaction followed by Maxam-Gilbert sequencing, to be the deletion of dinucleotide AA from the eight codone of beta-globin gene (the mutation is known to exist also in Turkey and Lebanon). Two other mutations have also been found in beta-globin gene of the same DNA, one of which (transversion C----G at position 16 of intron 2) eliminates the polymorphic AvaII-site and is associated with thalassaemia, and other is transition C----T in the third position of the second beta-globin codon.

Molecular nature of two beta 0-thalassaemia-causing mutations in beta-globin gene in Azerbaijanian population has been elucidated, viz., C-T transition in 39 codon (nonsense mutation) and previously unknown G deletion in 82/83 codons.