[Early diagnosis of risk for developing calcium oxalate urolithiasis].

AIM: To identify risk groups for calcium oxalate urolithiasis among healthy individuals and patients with urolithiasis in the Russian population using molecular genetics. MATERIALS AND METHODS: The study comprised 72 patients with calcium oxalate urolithiasis (study group) and 189 healthy adults from the general Russian population (control group). The study group consisted of 39 (54.2%) men and 33 (45.8%) women. The mean age of urolithiasis patients was 41.5+/-12.4 years. Analysis of polymorphic variants of 8 candidate urolithiasis genes: tumor necrosis factor 11B (TNFRSF11B, rs3134057), -subunit of the nuclear estrogen receptor (ESR1, rs851982), Cloto gene (KL, rs526906), vitamin D receptor (VDR, rs1540339 ), an extracellular calcium-sensing receptor (CASR, rs2202127), membrane anion transporter family 26 (SLC26A6, rs2310996), tumor necrosis factor 11 (TNFSF11, rs9525641), the calcium release-activated calcium modulator 1 (ORAI1, rs7135617) in two groups was performed by real-time PCR using Applied Biosystems test. Statistical analysis was performed using Fishers angular transformation and 2. RESULTS: In the polymorphism of the ORAI1 gene (rs7135617), the differences in the frequencies of the GG genotype and the G allele in the control sample and in the sample of patients with calcium oxalate urolithiasis were significant: p=0.0004 and p=0.001, respectively. No statistically significant differences in the genotype and allele frequencies were found in the remaining seven gene polymorphisms. CONCLUSIONS: Healthy individuals and patients with urolithiasis in the Russian population who have the GG genotype and/or the G allele of the polymorphism of the ORAI1 gene (rs7135617) represent risk groups for the formation of calcium oxalate stones.

[Comparative analysis of associations of polymorphic genes F2, F5, GP1BA and ACE with the risk of stroke development in Russian and Ukrainian populations].

The comparative analysis of the associations between G20210A polymorphism of F2 gene, G1691A polymorphism of F5 gene, -5T/C polymorphism of gene GP1BA, I/D polymorphism of gene ACE and the risk of development of the stroke in two ethnical samplings--Russian and Ukrainian populations--was conducted. It was shown that the patients of the Russian population with genotype DD have a higher level of the risk of ischemic stroke development (OR = 1.4, 95% CI [1.05; 1.78], p = 0.02), whereas genotypes I/I and I/D are associated with the lower level of risk of ischemic stroke (OR = 0.7, 95% CI [0.56; 0.95], p = 0.02). In the Ukrainian ethnical sampling, differences in distribution of genotypes and alleles frequencies between patients with stroke and healthy persons upon given polymorphic locus are not significant, and I/D polymorphism of gene ACE is not associated with the risk of development of the stroke (OR = 0.8, 95% CI [0.48; 1.32], p = 0.45). The G20210A polymorphism of gene F2, G1691A polymorphism of gene F5, -5T/C polymorphism of gene GP1BA are not associated with the risk of stroke in two ethnical samplings.

[Transcriptome alteration in hippocampus under the treatment of tuftsin analog Selank].

The effect of single and course administration of Selank (Thr-Lys-Pro-Arg-Pro-Gly-Pro) in the dose 200 microg/kg on the rat hippocampus transcriptional profile were studied using cDNA microarray technology. It was shown that mRNA levels of 36 genes changed more than 2-fold after a single intranasal Selank administration, and 20 genes--after course administration. It should be noted that most of them encode proteins associated with the plasma membrane (including transmembrane proteins). This suggests that Selank is able to regulate ion homeostasis of hippocampal cells and thereby modulate different ion-dependent processes, which include the processes of learning and memory formation.

[Association of rs10912745 and rs4916375 polymorphisms located in the cluster of flavin-containing monooxygenase genes, with ischaemic cardioembolic stroke].

Twenty-one SNPs located in the cluster of genes FMO1-FMO2-FMO3-FMO4 and adjacent areas were analyzed in the patients with ischaemic cardioembolic stroke and in the control group. Significant differences between these samples were found in the distribution of genotype and allele differences in two polymorphic loci, rs10912745 and rs4916375. It was shown that these polymorphic loci are associated with the risk of ischaemic cardioembolic stroke development.

[Association study of renin-angiotensin system genes and hemostasis system genes with ischemic stroke among Russians of Central Russia].

The analysis of alleles and genotypes frequencies of 14 SNP in genes of rennin-angiotensin system (REN, AGT, AGTR1, AGTR2, BKR2, ADRB2) and hemostasis system (FGB, F2, F5, F7, ITGB3, SERPINE1, MTHFR), as well as ACE insertion-deletion polymorphism in patients with stroke comparing to healthy controls matched by age, sex and ethnicity has been carried out. The genotyping procedure included the amplification of selected gene sequences following by hybridization of fluorescently labeled fragments with SNP-specific DNA probes. The analysis of allele frequencies of each gene separately revealed no statistically significant differences between groups of patients with stroke and healthy donors. Also the complex study has been performed to estimate the contribution of rennin-angiotensin system and hemostasis system genes to the genetic susceptibility to ischemic stroke among Russians from Central Russia using method MDR (Multifactor Dimensionality Reduction). The combination with increased risk for development of ischemic stroke was presented by complex genotype FGB G/- x ACE I/- x MTHFR C/- x SERPINE1 5G/5G (p = 0.03, OR = 2.4, 95% CI 1.1-5.3), which frequency was statistically significant higher in patients with stroke compared to healthy control.

[Association study of polymorphic markers of F12, PON1, PON2, NOS2, PDE4D, HIF1a, GPIba, CYP11B2 genes with ischemic stroke in Russian patients].

Allele and genotype frequencies of 10 single nucleotide polymorphisms in F12, PON1, PON2, NOS2, PDE4D, HIF1a,GPIba, CYP11B2 genes were studied in a group of Russian patients with ischemic stroke (IS) from central regions of the Russian Federation and healthy donors matched for sex, age and ethnicity. The genotyping procedure included the amplification of selected DNA sequences with the following hybridization of fluorescently-labeled regions with allele-specific DNA-probes immobilized on a biochip. An analysis of allele and genotype frequencies for each gene in IS patients and controls did not reveal any significant differences. The pair-wise comparison of genes demonstrated that the frequency of the combination PON1A/-x PON2 GG was higher in the group of patients (p=0.044, OR=3.4 95% CI 1.06 − 10.4) compared to the controls and, thus, was associated with the higher risk for stroke.

[The association between the DNA marker rs1842993 and risk for cardioembolic stroke in the Slavic population].

The analysis of association between DNA markers and total stroke risk was performed in 950 Slavonic patients. Patients with cardioembolic stroke were selected for a genome-wide association study. The HUMANCYTOSNP12 v.2 microchip was used to analyze all DNA samples on a panel of 301 000 single nucleotide polymorphisms. SNP rs1842993 on chromosome 7 was found to be associated with cardioembolic stroke risk.

[Analysis of the rs12720208 single-nucleotide polymorphism of the FGF20 gene in Russian patients with sporadic Parkinson's disease].

Parkinson's disease (PD) is a multifactorial neurodegenerative disease whose pathogenesis involves a number of genes and environmental factors. The FGF20 gene encoding the fibroblast growth factor and paying an important role neuron proliferation and survival is one of candidate genes of PD. There is evidence that this gene is also involved in the control of alpha-synuclein (SNCA) gene expression. The rs12720208 single-nucleotide polymorphism (SNP) in the FGF20 gene has been found to be associated with PD; it has been located to the 3'-UTR binding site for microRNA-433, which is involved in the control of FGF20 expression. Therefore, the frequency distribution of rs12720208 genotypes in the FGF20 gene has been analyzed in a sample of patients with sporadic PD and a control sample of the Russian population. The results have not shown any effect of rs12720208 in the FGF20 gene on the risk of PD in patients residing in Russia (OR = 0.95, the 95% confidence interval (CI) is 0.55-1.63, p = 0.9).

[Analysis of the polymorphic variants of the PDE4D gene in patients with acute stroke in the Moldavian population].

The risk of the ischemic stroke is mediated by both environmental and genetic factors. Recent studies of DeCode group identified the risk of polymorphisms for ischemic stroke in the phosphodiesterase 4D gene (PDE4D). The goal of this study was to explore the role of two variants of the gene encoding PDE4D [SNP41 (rs152312) and SNP87 (rs2910829)] in the Moldavian patients with ischemic stroke and in control. No significant association with ischemic stroke was observed with SNP41 and 87.

[Changes in expression of the genes for chemokines, cytokines, and their receptors in response to selank and its fragments].

A study of the immunomodulating effect of selank showed that the total peptide and its fragment significantly change the expression of the genes for chemokines, cytokines, and their receptors in mouse spleen 6 and 24 h after administration of a single dose. Changes in the mRNA level of the majority of the genes under study were similarly observed after the administration of Gly-Pro, which was earlier identified as a selank pharmacophor, a minimum fragment with anitiviral activity. Pharmacological preparations based on endogenous regulatory peptides are studied intensely because they are the most promising class of drugs and have almost no side effects. The class includes selank, which is a synthetic analog of taftsin. Selank exerts anxiolytic and nootropic effects and, on the other hand, has pronounced antiviral properties.

[Analysis of single nucleotide polymorphism rs415430 in the WNT3 gene in the Russian population with the Parkinson disease].

The Parkinson disease (PD) is the second most common progressive neurodegenerative disorder that arises due to degeneration of dopaminergic neurons. The causes of this disease are still unknown, but a number of genes involved in pathogenesis of familial and sporadic forms of PD has been identified. According to recent data of genome wide association studies (GWAS), single nucleotide polymorphisms (SNPs) in these genes (including MAPT locus) may play an important role in the development of PD. Therefore, we analyzed distribution of genotype frequencies of SNP rs415430 in the WNT3 gene in the Russian patients with sporadic PD and in the Russian population controls (OR = 0.84, Confidence Interval (95% CI) 0.58-1.23, p = 0.39). It was concluded that SNP rs415430 in the WNT3 gene was not associated with the risk of development of PD.

[Expression of GSK3B gene in peripheral blood in patient with Parkinson's disease].

Parkinson's disease (PD) is the second most common progressive neurodegenerative disorder characterized by the degeneration of dopaminergic neurons. Detecting changes in gene expression in untreated de novo patients with PD is important for understanding disease pathogenesis and for identifying biomarkers for preclinical stage of PD. In this study we investigate expression of gene of Glycogen synthase kinase-3 beta (GSK3B) in the peripheral blood of different groups of patients with neurological diseases using reverse transcription reaction and real-time polymerase chain reaction (PCR). Our results suggest that the expression levels of GSK3B can't serve as a biomarker for early stages of PD.

[Polymorphic variants of ALOX5AP gene and the risk of acute stroke development in the Russian population].

A protein capable of activating 5-lipoxygenase (ALOX5AP) is considered a presumable risk factor of acute stroke development. Polymorphic variants of the ALOX5AP gene were examined. Two ALOX5AP gene polymorphisms (SG13S114 (rs10507391) and SG13S32 (rs9551963)), which previously had shown association with the risk of ischemic stroke in other populations, were studied. These single nucleotide polymorphisms were analyzed using a sample of acute stroke patients (N = 1320) and a control sample (N = 467). No statistically significant associations were found between acute stroke and the ALOX5AP gene polymorphisms examined.

[Transcranial sonography in Parkinson's disease].

An abnormal hyperechogenecity of substantia nigra is thought to be the most characteristic sonographic feature in Parkinson's disease (PD). However specificity and sensitivity of the ultrasound method should be refined. Using transcranial sonography, authors have examined 168 patients with different clinical signs of parkinsonism, including 99 patients with idiopathic PD, and 56 patients without extrapyramidal disorders. Hyperechogenecity of substantia nigra was found in 93% of patients and in 14% of controls. It has been shown that this biomarker can successfully discriminate PD from a number of similar disorders (essential tremor, atypical parkinsonian syndromes). Sonographic features of late, early and genetically determined parkinsonism specifying some pathogenetic aspects of these pathologies are described. Taking into account the data obtained, transcranial sonography can be considered as a highly informative method in the differential and early diagnosis of PD.

[Association of cerebral stroke with a phosphodiesterase 4D (PDE4D) gene polymorphism in the Moscow population].

We studied SNP41 (rs152312) and SNP87 (rs2910829) of the PDE4D gene in 577 stroke patients and 270 healthy controls. The significant differences in the distribution of genotype and allele frequencies of the SNP41 between patients and controls were revealed. Genotypes AA and AG were associated with the higher risk of stroke in the Moscow population (OR 1,6). No association between SNP87 and stroke was found.

[Analysis association of acute ischemic stroke and DNA markers in Russian and Moldavian populations].

Polymorphisms c.202G > A of prothrombin F2 gene, c.1691G > A of coagulation factor V F5 gene, c.675delinsG of plasminogen activator1 gene, and (-5)T > C Kozak gene of thrombocytic receptor were studied in the Russian and Moldavian ethnic groups. We have found no association between these polymorphisms and the risk of ischemic stroke development in both ethnic groups. No association was revealed between the risk of stroke development and various combinations of the single nucleotide polymorphisms examined in the sample of ischemic stroke patients from Russia.

[The role of polymorphic variants of gene of inducible NO-synthase NOS2 in brain infarction in patients with acute ischemic stroke].

Cerebrovascular diseases including stroke are an important problem of public health. Stroke development depends on external factors and individual genetic specificity of patient. Excessive NO production by inducible NO-synthase (iNOS) damages brain tissue at various stages of the disease. The goal of this work was to study the role of 4 polymorphic variants of gene of inducible NO-synthase iNOS (-2447C/G, -1659C/T, -0,7(OTTA)n I/D, S608L (150C/T)) in brain infarction in patients with acute ischemic stroke. A statistically significant correlation between S608L (150C/T) polymorphism and infarction dynamics was observed during days 1-3 and 7-21 after infarction. These parameters correlated with neurological status estimated using the Orgogozo scale during days 1-7 of the disease development. It was demonstrated that genotype N150N was associated with ischemic focus propagation regardless of its volume and neurological status by Orgogozo scale in patients with acute stroke. It was also observed that genotype N150N had effect on ischemic damage during days 1-3 in case of low initial volume.

[Phosphodiesterase 4D (PDE4D) gene polymorphism in patients with acute stroke from Moscow].

Two PDE4D gene polymorphisms [SNP41 (rs152312 and SNP87 (rs 2910829)] were studied in patients with acute stroke (n = 577) and in control sample (n = 270). Significant differences in the genotype and allele frequency distribution were found between these samples for polymorphism SNP41. We showed that the AA and AG genotypes of SNP41 polymorphism were associated with higher risk of acute stroke development in the Moscow population (OR = 1.6). No association of SNP87 polymorphism with the disease was observed.

[Analysis of the alpha-synuclein gene dosage variation associated with autosomal dominant form of ParkinsonTs disease].

Fifty-two patients that had ParkinsonTs disease with autosomal dominant type of inheritance were analyzed for the presence of duplications and triplications in exons 4--6 of alpha-synuclein gene using real-time PCR with Taq-Man probes. No mutations involving the examined exons dosage were revealed in alpha-synuclein gene. Thus, mutations modifying copy number of alpha-synuclein gene do not significantly affect the pathogenesis of the autosomal dominant form of ParkinsonTs disease in patients from Russia.