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Biomedical subjects

P A Slominskiĭ

Publications and source records attributed to P A Slominskiĭ.

At least 19 recordsLinked to original sources
PubMed2006

[Detoxication gene polymorphism and susceptibility to sporadic motor neuron disease in Russian population].

Motor neuron disease (MND) is caused by selective degeneration of motor neurons of the cerebral cortex, brain stem and spinal cord. Many genetic systems are thought to be involved in pathogenesis of this complex disease. A significant etiological factor of MND may be oxygen free radicals, which damage neuronal cells when they are present in high concentrations. Detoxication processes resulting in the formation of free radicals, which subsequently transformed into nontoxic products, are also critical for the disease development. The major participants of these processes are cytochromes P-450 (CYP2E1, CYP2D6), glutathione-S-transferases (GSTM1, GSTT1, GSTP1) and N-acetyltransferases (NAT2). To investigate a role of genes of detoxication system in development of MND, we study polymorphisms in these genes in 72 patients with MND from Moscow and controls from Russia. Significant statistical differences have been found in frequency of the alleles CYP2E1*1D, CYP2D6*4 and GSTM1(0/0) and genotypes homozygous for GSTM1 (0) between the study and control groups. The analysis of GSTT1, GSTP1 and NAT1 gene polymorphisms has revealed no between-group differences in distribution of different alleles and genotypes. The GSTP1*A/ GSTP1*A genotype was associated with a classical upper and lower motor neuron involvement and the GSTP1*A allele with predominant lower and upper motor neuron involvement.

Alleles↗
PubMed2006

[Analysis of the possible involvement of the glutamate transporter gene EAAT2 and the glutamate receptor genes GRIA1 and GRIA2 in pathogenesis of motor neuron disease in the Russian population].

Polymorphisms of the genes of the glutamatergic system EAAT2, GRIA1, and GRIA2 have been analyzed in patients with sporadic motor neuron disease (MND) from Russia. The disease is not associated with polymorphic alleles of the genes studied, which indicates that EAAT2, GRIA1, and GRIA2 play an insignificant role in the pathogenesis of sporadic MND.

Alleles↗
PubMed2006

[Molecular genetics of Parkinson's disease].

The current views on the role of genetic factors in the pathogenesis of Parkinson's disease are considered. The review is focused on monogenic forms of the disease, for which 11 loci are mapped and seven genes whose mutations cause the disease are identified. In addition, a number of candidate genes for sporadic Parkinson's disease are described. The further development of studying genetic bases of Parkinson's disease will follow two main directions: in-depth analysis of genes related to the monogenic form of the disease and more large-scale associative investigation of candidate genes for the sporadic form of Parkinson's disease.

Chromosome Mapping↗
PubMed2004

[Molecular genetic analysis of hereditary neurodegenerative diseases].

The review summarizes the results of a decade of molecular genetic studies of several high-incidence hereditary neurodegenerative diseases, including primary parkinsonism, various forms of hereditary dystonia and ataxia, polyglutamine disorders, hepatolenticular degeneration, essential tremor, etc. Various relevant mutations were studied. The character and frequencies of particular mutations and the corresponding genetic disorders were established for the Russian population. Particular genotypes were associated with various clinical variants of the diseases. Genetic loci were identified for several unique hereditary diseases of the nervous system (X-linked cerebellar hypoplasia, an atypical form of autosomal recessive muscular dystrophy, etc.). Nosological positions of the relevant clinical forms were clarified on the basis of the molecular genetic data. Protocols were developed for direct or indirect DNA diagnostics of the diseases under study to improve medical genetic counseling and prevention of new disease cases in affected families.

Genetic Diseases, Inborn↗
PubMed2004

[Analysis of the glutathione S-transferase P1 gene Ile105Val polymorphism in the patients with sporadic motor neuron disease from Russia].

Ile105Val polymorphism in exon 5 of glutathione S-transferase (GSTP1) gene was examined in a group of patients with motor neuron disease (MND) and control sample. No statistically significant differences in the allele and genotype frequency distributions between the samples examined were demonstrated. We conclude that Ile105Val polymorphism is not associated with the risk of the disease development in the patients from Russia with sporadic form of MND.

Alleles↗
PubMed2004

[Clinical and genetic analysis of juvenile parkinsonism in Russia].

Clinical and genetic analysis of juvenile parkinsonism was performed in 26 sibs from 20 families. Heterogeneity of the disorder was observed. Mutations in the parkin gene (locus PARK2, chromosome 6q25.2-27), with the prevalence of deletions over point mutations, have been identified in 41%. The comparative clinical analyses of patients examined confirmed the phenotypical polymorphism of "parkinopathy". We also showed the absence of asymmetric manifestation--an important and underestimated so far sign of the disease. The results of the study may be considered as a valuable clue to the clinical diagnosis of parkin-related juvenile parkinsonism in Russian population and implemented for mutation screening and medico-genetic counseling of affected families.

Adolescent↗
PubMed2003

[Role of missense mutation (M235T) in the angiotensinogen gene in development of cerebral ischemia].

Possible correlation of M/T polymorphism of angiotensinogen gene with risk of ischemic stroke and basic risk factors of cerebral pathology (levels of arterial pressure and blood cholesterol; presence of diabetes mellitus, coronary heart disease, or myocardial infarction in anamnesis; and stenosis of major cerebral arteries) was studied. It was shown that M/T polymorphic variants of angiotensinogen gene were factors determining neither clinical variant of cerebral ischemia development (acute ischemic stroke or chronic brain ischemia) nor formation of main risk factors of stroke.

Aged↗
PubMed2003

[Analysis of deletion mutations in the PARK2 gene in idiopathic Parkinson's disease].

A method for analysis of deletions and duplications of individual exons and groups of exons in the parkin gene (PARK2) in both homozygous and heterozygous states has been developed. The method is based on semiquantitative polymerase chain reaction (PCR). The method has been used for analysis of the frequency of deletions in gene PARK2 in patients with idiopathic Parkinson's disease from Bashkortostan. Two unrelated patients have been found to carry a deletion of the 12th (last) exon of gene PARK2. Possibly, this deletion has caused the disease in the given patients.

Bashkiria↗
PubMed2003

[Association of homozygosity for short allele (S) of heavy neurofilament subunit gene with motor neuron disease and oxidative stress development].

We analyzed distribution of heavy neurofilament (NF-H) gene S/L-polymorphic variants in 51 patients with idiopathic motor neuron disease (MND) vs control group and in relation to superoxide dismutases (SODs) activity and thiobarbituric acid reactive substances (TBARS) level in cerebrospinal fluid (CSF), erythrocytes and blood serum. We found that individuals with homozygosity for NF-H gene short allele (S/S-genotype carriers) in MND group predominate significantly over those in control one (p < 0.001). We revealed significant increase of oxidative markers in CSF and blood serum in MDN patients vs controls (p < 0.05), but not in patients with spondylogenic myelopathy, conforming non-specific role of oxidative stress in MND pathogenesis. There were no differences between TBARS level in CSF and serum in relation to the rate of MND progression, suggesting that oxidative stress does not influence the MND course. We showed normal SOD-1 activity in erythrocytes and CSF of MND patients that argued for the absence of these antioxidant enzymes deficiency in MND without SOD-1 gene mutations. We found significant association between homozygosity for short allele (S) and increased TBARS level in CSF (p < 0.02). These findings specify the role of NF-H with lower molecular weight in MND pathogenesis and make expedient antioxidants administration to MND patients homozygous for S-allele of NF-H gene.

Alleles↗
PubMed2003

[The role of polymorphic variants of renin-angiotensin system genes in the development of ischemic stroke in Moscow population].

Polymorphic variants of genes for angiotensin-converting enzyme (ACE) and angiotensinogen (ATG) were studied in 110 patients with different types of brain ischemic disease--carotid atherothrombotic ischemic stroke (one of the pathogenic brain infarction variants) as well as in 119 their siblings with the main risk factors of cerebrovascular pathology development being taken into account. No association has been found between ACE and ATG genes polymorphisms and carotid atherothrombotic ischemic stroke. However, the presence of a homozigous DD ACE genotype was shown to be an independent risk factor for development of hemodynamically relevant stenosis of the major brain arteries. The absence of differences in genetic variants distribution in patients with acute ischemic stroke, comparing to those with prolonged chronic brain ischemic disease (without infarction formation) and the highest frequency of this polymorphism in "longevity" group (without lifetime stroke) imply a relatively independent character of the atherothrombogenic process, which may probably underlie a further development of pathological process.

Aged↗
PubMed2003

[Association between Bam HI RFLP p53 gene polymorphism and brain infarction volume in patients with atherothrombotic ischemic stroke].

A significant association between Bam HI RFLP p53 gene polymorphism and brain infarction volume in patients with atherothrombotic ischemic stroke (AIS) from Moscow population was found. Biallelic Bam HI polymorphism in exon 5 of p53 gene was studied in 96 AIS patients, 100 their healthy siblings, 41 patients with chronic ischemic disease and 42 their healthy siblings. Magnetic resonance tomography with morphometric program "Osiris" (the Hospital of the University, Geneva) for infarction volume measuring was used on day 1 and 7 after stroke onset. The patients with (-/-) p53 Bam HI genotype had the smaller brain infarction sizes (< 40 cm3), comparing to those with (-/+) (chi 2 = 19.7; p < 0.001) and (+/+) (chi 2 = 12.3; p < 0.001) genotypes. According to Bayes statistics, development of smaller infarction size in AIS may be predicted with over than 65% probability in the patients with (-/-) p53 Bam HI genotype. A significant association between p53 Bam HI polymorphism and infarction volume in patients with carotid atherothrombotic stroke confirms an important role of apoptosis in ischemic brain lesions formation that demands temporary antiapoptotic influence on patients with stroke.

Aged↗
PubMed2003

[Peculiarities of sporadic motor neuron disease associated with D90A and G12R mutations in Russian population].

Fifty-one blood samples of Russian patients with sporadic motor neuron disease were examined for mutations in Cu/Zn superoxide dismutase (SOD-1) gene. One female patient with amyotrophic lateral sclerosis (ALS) was heterozygous for G12R mutation. This patient suffered from ALS with cervical cord onset, pyramidal variant and fast progression. Mutation was also detected in her healthy son. Earlier, such mutation was described in 5 Italian patients with slow progressive ALS. Also, D90A SOD-1 gene associated haplotypes of the female ALS patients previously examined by the authors have been analyzed. A homozygous female patient with ALS was characterized by typical lumbar onset and extremely slow progression, as well as a female patient with heterozygous mutation and moderate progression carried so-called "Scandinavian" haplotype. To our knowledge, it is the first report on the finding of the haplotype considered as a "protective" one in the subjects heterozygous for D90A mutation with clinical symptoms of ALS. Mechanisms of "protective" influence of this haplotype on ALS course are not yet elucidated. Our finding suggests that the presence of "Scandinavian" haplotype does not completely protect from the disease development in patients exposed to other more pathogenic causative factors. This assumption is in line with modern conceptions on motor neuron disease as a complicated multifactor disorder.

Aged↗
PubMed2002

[Polymorphism of the STR-locus of Y chromosomes in Eastern Slavs in three populations from Belorussia, Russia and the Ukraine].

Allelic polymorphism of five microsatellite loci of the human Y chromosome (DYS19, DYS390, DYS391, DYS392, and DYS393) was analyzed in samples of male populations from Ukraine, Russia, and Belarus (152 subjects in total). The allelic diversity indices (Dg) were determined for all loci; they varied from 0.23 to 0.72. The mean values of this parameter in the Ukrainian, Russian, and Belarussian populations were 0.45, 0.47, and 0.52, respectively. A total of 53 different haplotypes were found in 152 subjects from three populations. The most frequent haplotype was found in 14.5% of the subjects, whereas 35 haplotypes (23%) were each found in only one person. The haplotypic diversity index (Dhp) was 0.94. The genetic distances between the populations studied and some populations of Western and Central Europe were estimated. These data were used to construct a phylogram (tree) of genetic similarity between the populations, which demonstrated that the three Eastern Slavic populations are genetically close to one another and remote from Western European populations.

Base Sequence↗
PubMed2002

[Polymorphism of glutathione S-transferases M1 and T1 in several populations of Russia].

Frequencies of the wild-type and null genotypes of the GSTM1 and GSTT1 genes were established in healthy donors from several Russian populations (ethnic Russians from the towns of Oshevensk and Kholmogory, Arkhangel'sk oblast; ethnic Khants; ethnic Kalmyks; and ethnic Buryats) in order to identify the ethnic group with the maximal frequency of the null genotype. The highest frequency of individuals with the null genotype of both genes was observed in the Kalmyk and Buryat populations. The results may be used to study the effect of climatic and ecological conditions on multifactorial disease incidence in populations.

Genetics, Population↗
PubMed2002

[CTG-repeat analysis of myotonin protein kinase gene in Bashkortostan patients with myotonic dystrophy].

A DNA analysis of 72 patients from Bashkortostan clinically diagnosed with myotonic dystrophy and 54 their family members was conducted. CTG-repeat expansion in the myotonin proteinkinase gene was found in 67 (92%) patients and 12 their relatives without clinical symptoms of the disease at the moment of examination. A correlation between the most distinct clinical symptoms and CTG-repeat number has been studied. A CTG-repeat expansion in generations was compared to that in sib pairs with myotonic dystrophy. In 17.6% of the cases, CTG-repeat number decreased in the following generations and in 11.7% it did not change, the percentages being higher than those described elsewhere. In general, anticipation phenomenon was confirmed for CTG-repeat in myotonin proteinkinase gene.

Adolescent↗