[The genes of atherosclerosis and cardiovascular diseases].

The aim of the work was to study polymorphism of atherosclerosis-related genes in patients with different forms of coronary heart disease (CHD) and chronic cerebral ischemia (CCI) in comparison with long-living subjects. Analysis included the distribution of genotypes and alleles of functional polymorphisms of lipid metabolism genes, viz. HindIII--polymorphism of lipoproteinase (LPL) gene; HhaI--polymorphism of apoE gene; TaqIB--polymorphism of cholesterol ether transfer protein (CETP) gene; I/D--polymorphism of angiotensin converting enzyme (ACE) in CHD and CCI patients of different age groups including long livers and those presenting with different clinical variants of CHD and CCI (FC II-III stable angina of effort, acute myocardial infarction, post-infarction cardiosclerosis, acute coronary syndrome) and control subjects. The study revealed potential molecular-genetic markers for primary and secondary prophylaxis of CHD and CCI. It was shown that DD genotypes of ACE gene, H+/+ of LPL gene and E3E4 are associated with an enhanced probability of myocardial infarction (IM) in CHD patients and can be regarded as high risk markers. The DD genotype is associated with an increased risk of recurrent MI, life-threatening post-IM complications and severe cardiac insufficiency as well as peculiar personality and behavioural traits (animosity and type A behaviour)--psychological risk factors of CHD and predictors of delayed application for medical aid. E2 allele of the ApoE gene and H allele of the LPL gene occur much more frequently in CHD patients aged above 90 years (long livers) than in younger subjects; hence, their value as markers of stable ischemic disease. Protective effect in terms of favourable clinical course of CCI and life expectancy is especially pronounced in subjects with a combination of genotypes with E2E3 + H+H-, E2E2 + H+H-, E3E3 + H-H-genes of ApoE and LPL. B2B2 genotype of CETP gene increases the risk of stable CCI and B1B1 genotype of CETP gene enhances predisposition to cardiovascular pathology.

[The relation between gene of lipoprotein-lipase and carrier protein of cholesterol ethers and life duration in patients with chronic cerebral ischemia].

Comparative analysis of frequency distribution of genotypes and alleles of HindIII-polymorphism of gene LPL and TaqIB-polymorphism of gene CETP in 267 patients of various ages with chronic cerebral ischemia (CCI) was performed. Relation between age and polymorphous variants of genes LPL and CETP was noticed. It was shown that genotype of H+H+ HindIII-polymorphism of and genotype B1B1 TaqIB-polymorphism of gene CETP were found more frequently in more young patients with chronic cerebral ischemia (CCI). Since there is an association of these genotypes with atherogenic dislipidemias, they apparently can be considered as risk factors of CCI development. On the contrary, genotype of gene LPL and B2 allele of gene CETP in patients elder 90 years (long-livers) are found significantly more frequently than in younger patients, that makes possible to consider they as markers of favorable course of disease and patients' long life.

[ACE gene I/D-polymorphism and hereditary predisposition to myocardial infarction]. / Sviaz' I/D-poliformizma gena angiotenzinprevrashchaiushchego fermenta s nasledstvennoi predraspolozhennost'iu k infarktu miokarda.

The authors compare distribution of genotype frequencies and alleles of I/D of ACE gene polymorphism in patients with various forms of ischemic heart disease (IHD): with acute myocardial infarction (MI), stable effort angina (functional class II-III); in patients with postinfarction cardiosclerosis (PICS). A relationship was found between I/D polymorphism and acute MI. Frequency of DD genotype in MI patients was 0.57, in controls--0.21, p < 0.0001, RR = 4.9. The DD genotype may serve a marker of hereditary predisposition to MI. Genotype DD frequency in the group with acute MI was higher than that with PICS. In acute MI frequency of allele D was 0.76, in PICS--0.51, p < 0.0005. It is suggested that low frequency of genotype DD in the PICS group results from higher lethality of patients with DD genotype in the nearest rehabilitation period. Patients with repeated MI have a significantly higher frequency of genotype DD and complications after MI. Thus, there is a relationship between insertion-deletion polymorphism of ACE gene and myocardial infarction. Deletion DD genotype raises the risk to develop MI and probability of life-threatening complications and repeated MI.

[HindIII DNA-polymorphism of lipoprotein lipase gene in elderly patients with ischemic heart disease]. / HindIII DNK-polimorfizm gena lipoproteinlipazy u bol'nykh ishemicheskoi bolezn'iu serdtsa pozhilogo vozrasta.

AIM: To determine incidence of HindIII alleles of lipoprotein lipase (LPL) in Russian elderly patients with stable effort angina (SEA) functional class II-III regarding lipid metabolism. MATERIAL AND METHODS: Genotyping by LPL gene was performed in 103 patients with SEA. Of them 13 patients survived myocardial infarction (MI), 29 patients had diabetes mellitus. RESULTS: Incidence of alleles of HindIII DNA-polymorphism of LPL gene both in healthy and IHD patients is comparable with that in the West European populations. CONCLUSION: Genotype H+H+ of LPL gene is one of the markers of predisposition to MI, while allele H- is one of the resistance marks.

[Connection of HindIII-polymorphism in the lipoprotein lipase gene with myocardial infarct and life span in elderly ischemic heart disease patients]. / Sviaz' HindIII-polimorfizma v gene lipoproteinlipazy s infarktom miokarda i prodolzhitel'nost'iu zhizni u bol'nykh ishemicheskoé bolzn'iu serdtsa pozhilogo i starcheskogo vozrasta.

Allele and genotype frequencies of the HindIII polymorphism of the lipoprotein lipase (LPL) gene were studied in patients with myocardial infarction (MI) and stable angina of effort (SAE), including long-lived people (over 90). The polymorphism proved to be associated with MI and with the life span, genotype H+/H+ being predisposing to MI and allele H- being protective. The allele and genotype frequencies of long-lived people differed significantly from the Hardy-Weinberg proportions and from those of SAE patients aged up to 90. An excess of heterozygotes in this group suggests a selective pressure which eliminates homozygotes. Possibly, heterozygotes H+/H- have an adaptive advantage, which provides for their longevity.

[DNA-diagnosis of bulbospinal muscular atrophy (Kennedy's disease)]. / DNK-diagnostika bul'bospinal'noi myshechnoi atrofii (bolezn' Kennedi).

Bulbospinal muscular atrophy--a rare disease with X-linked recessive type of inheritance. It is caused by expansion of trinucleotide repetitions in the gene of androgenic receptor (AR). We elaborated a method of DNA-testing with usage of nonradioactive registration of mutant alleles of AR gene. DNA-diagnosis was performed in 16 patients with clinical pattern of bulbospinal muscular atrophy and diagnosis was confirmed in 11 patients. Carriage of mutant alleles was found in 7 women--relatives of the patients. Presymptomatic diagnosis revealed the presence of mutant alleles in 2 boys. Unstability of alleles of mutant AR gene was observed in one family: in sons there was more (upon 5) of CAG-triplets.

Prenatal diagnosis of spinal muscular atrophy in Russia.

Ninety-two families with spinal muscular atrophy (SMA) applied for genetic counselling and further prenatal diagnosis. To minimize expenses, only one tightly linked informative marker was determined in the course of preliminary examination, and non-radioactive allele detection was preferably used. Four prenatal diagnoses of SMA type I, four of SMA type II, and one of SMA type III were made. This trial programme shows the considerable requirements, importance, and potential effectiveness of prenatal prediction of SMA in Russia.

[Screening for deletion in patients with Duchenne's myodystrophy by multiplex amplification]. / Skrining deletsii u bol'nykh miodistrofiei Diushenna metodom mul'tipleksnoi amplifikatsii.

Patients with Duchenne muscular dystrophy were analyzed using the method of polymerase chain reaction in order to reveal deletions in the dystrophin gene. Deletions of different lengths and locations were detected in 28 of 78 ill boys. The highest number of deletions was detected in the 3'-end of the gene (the 45-50th exons).

[Analysis of deletions in the dystrophin gene by the multiplex amplification method in patients suffering from Duchenne's muscular dystrophy]. / Analiz deletsii v gene distrofina metodom mul'tipleksnoi amplifikatsii u patsientov, stradaiushchikh miodistrofiei diushenna.

Multiplex polymerase chain reaction was carried out with the material from 68 patients suffering from Duchenne muscular dystrophy in Moscow and Leningrad clinics. Six pairs of oligoprimers were used. Deletions were detected in the material from 22 patients. A new type of deletion was found. Data on deletion frequencies and spectrum were compared with the results published by other authors.

[Prenatal DNA-diagnosis of Duchenne muscular dystrophy]. / Prenatal'naia DNK-diagnostika miodistrofii Diushenna.

Two prenatal diagnoses were carried out by the technique of intragenic polymorphous marker detecting heterozygosity in pregnant women in the families with cases of Duchenne muscular dystrophy. In both cases the DNA fragment from pERT87-15 region was amplified. This fragment includes a polymorphous site in BamHI region of recognition. DNA analyses of the families members have been made and the genetical risk has been calculated by the Bayes method. The prognoses for both fetuses are good.

[The preclinical DNA diagnosis of Huntington's chorea]. / Preklinicheskaia DNK-diagnostika khorei Gentingtona.

Presymptomatic DNA diagnosis of Huntington's chorea (HC) was made for two sons of a patient affected with the disease using amplification of the DNA fragment in the area of locus G 8 linked with HC gene. That fragment contains a polymorphous site in the area of restrictase recognition Hind III, being of information value as regards the family under examination. The familial analysis with the use of the DNA diagnosis data makes it possible to exclude the inheritance of HC gene for both the sons of the patient with a probability of 96%.

[A benign variant of the course of Duchenne muscular dystrophy in a child with short stature]. / Dobrokachestvennyi variant techeniia miodistrofii Diushenna u rebenka s nizkoroslost'iu.

The authors describe a case of a benign variety of progressive Duchenne type muscular dystrophy in a 8-year-old short-stature boy. Provide the electromyographic and electroneuromyographic data, measurements of the growth hormone in blood serum and osseous age. Make suggestions about coupled inheritance of progressive Duchenne type muscular dystrophy and short stature . The latter one is likely to be attended by a decrease of anabolic processes, which may determine a more benign course of the myodystrophic process.

[DNA-diagnosis of carriers of the Duchenne muscular dystrophy gene]. / DNK-diagnostika nositel'stva gena miodistrofii diushenna.

Duchenne muscular dystrophy carrier detection has been performed by using probes XJ1.1 (intragenic probe) and probe 754 for a girl. The carrier probability was estimated by means of a computer program GenRisk combining pedigree and DNA-probe data and turned out to be 95%.

[Carrier detection and prenatal diagnosis of Duchenne's muscular dystrophy based on DNA analysis]. / Ustanovlenie nositel'stva i prenatal'naia diagnostika miodistrofii Diushenna na osnove analiza DNK.

Seven families with histories of Duchenne's muscular dystrophy underwent DNA diagnosis. The daughters of those consulted were examined for the carriage in 4 families. Their carriage was rejected or confirmed. Prenatal diagnosis was made in 2 families. In another family an abortion preceded obtaining molecular-genetic evidence. Probes 754, p20, XJI.I and primers for amplification of the site pERI87-15 containing a polymorphic locus were employed. The genetic risk was assessed using the computer program GenRisk adjusted for family history and DNA test allowances.

[Mitomycin C induced structural changes in heterochromatic regions of human chromosomes 1, 9, 16 and Y]. / Indutsirovannye mitomitsinom C strukturnye izmeneniia geterokhromaticheskikh raionov khromosom 1, 9, 16 i Y cheloveka.

Aberrations and variations in the heterochromatic blocks of chromosomes 1, 9, 16 and Y were found under the influence of mitomycin C in cultured lymphocytes of peripheral human blood. Lymphocytes were cultured during 96 hours, mitomycin C in final concentration of 0.3 mkg/ml was present in the culture during the latest 24 hours of culturing. Different changes in the heterochromatic regions of chromosomes were found in approximately 30% of cells: in 6.3% of cells mitotic chiasmata were indicated. In 9.5% of cells isolocus breaks were observed in heterochromatic region of chromosome 1 in segment 1q11. In the latter case this may be a fragile site detected under the influence of mitomycin C on the lymphocytes.

[Spontaneous level of sister chromatid exchanges in patients with tuberous sclerosis and Recklinghausen's neurofibromatosis]. / Spontannyi uroven' sestrinskikh khromatidnykh obmenov u bol'nykh tuberoznym sklerozom i neirofibromatozom Reklingauzena.

It is shown that the average number of sister chromatid exchanges (SCE) per one cell in patients with tuberous sclerosis as well as in those with Recklinghausen's neurofibromatosis do not differ from the control. But the non-parametric methods of analysis have revealed differences in the spontaneous level of SCE is patients with tuberous sclerosis, while no such differences were revealed in patients with Recklinghausen's neurofibromatosis.