ABSTRACT
A total of 16 to 60% of individuals in human populations are homozygous with respect to a deletion of the Glutathione-S-transferase M1 gene. In this study, we evaluated the relationship between the GSTM1 gene deletion and genetic diversity of the GSTM cluster, which includes this gene, in three Russian populations. The study was based on the comparison of the haplotype distribution in two groups of individuals subdivided accordingly to the presence of the deletion. The first group included individuals with completely deleted GSTM1 gene, and the second group comprised individuals having at least one functional variant of GSTM1 gene. The analysis of the haplotype frequencies in groups revealed no specificity in their distribution both within the populations and between them.
Subject(s)
Gene Deletion , Glutathione Transferase/genetics , Haplotypes , Multigene Family , Female , Humans , Male , Russia/ethnologyABSTRACT
Biologically active regulatory peptide, tripeptide Pro-Gly-Pro (PGP) was used as C-terminal fragment for peptide drugs Semax and Selank. In recent years the independent effects of PGP were observed. The question was raised, whether PGP contributes to the effects ofpeptide drugs containing PGP as a fragment. The genome-wide analysis was performed to investigate the influence of PGP on the transcriptome of ischemic rat brain cortex tissues. The gene expression alterations caused by the action of the tripeptide PGP were compared with the gene expression of the control group "ischemia" at 3 and 24 h after permanent occlusion of left middle cerebral artery. The altered expression was detected for 29 genes at 3 h and 57--at 24 h. The proteins encoded by these genes have variety of functions: cytokines, transport proteins, transcription factors, transmembrane receptors, etc. Biological processes, which are related to the genes with altered expression, were distinguished. The influence of PGP on the diversity of biological processes in different systems of the organism is demonstrated for the first time. The process "Immune response" was the most statistically notable at 24 h after occlusion. The expression of the immune system genes was predominately down regulated.
Subject(s)
Brain Ischemia/genetics , Cerebrovascular Disorders/genetics , Gene Expression Regulation/drug effects , Neuroprotective Agents/pharmacology , Oligopeptides/pharmacology , Proline/analogs & derivatives , Transcriptome , Animals , Brain Ischemia/immunology , Brain Ischemia/pathology , Carrier Proteins/genetics , Carrier Proteins/immunology , Cerebral Cortex/drug effects , Cerebral Cortex/metabolism , Cerebral Cortex/pathology , Cerebrovascular Disorders/immunology , Cerebrovascular Disorders/pathology , Cytokines/genetics , Cytokines/immunology , Gene Expression Profiling , Immunity, Innate/drug effects , Male , Proline/pharmacology , Rats , Rats, Wistar , Receptors, Cell Surface/genetics , Receptors, Cell Surface/immunology , Transcription Factors/genetics , Transcription Factors/immunologyABSTRACT
Vascular endothelial growth factor (VEGFA) is a hypoxia-inducible signal glycoprotein. VEGFA causes vascular endothelial cell growth and proliferation, that leads to the regeneration of vascular network in brain regions damaged by ischemia. However, this protein is involved in processes of inflammation and edema in early stages of ischemia. Synthetic peptide semax shows neuroprotective and anti-inflammatory properties and is actively used in the treatment of ischemia.We have previously shown that semax reduces vascular injury and activates the mRNA synthesis of neurotrophins and their receptors under global cerebral ischemia in rats. Here we have analyzed the effects of semax and its C-terminal Pro-Gly-Pro tripeptide upon Vegfa mRNA expression in different rat brain regions after common carotid artery occlusion. The animals were decapitated 30 min, 1, 2, 4, 8, 12, 24 h after the operation. It was shown that ischemia increases levels of Vegfa mRNA in the rat brain of animals (4 h after the occlusion--in the cerebellum, cerebral cortex and hippocampus, 8 h--in the cortex and hippocampus, and 24 h in the cortex). Semax treatment reduces Vegfa mRNA levels in the frontal cortex (4, 8 and 12 h after the occlusion) and hippocampus of ischemic rats (2 and 4 h). Effect of PGP on the Vegfa gene expression was almost negligible. Our results showed that semax prevents activating effect ofhypoxia on the Vegfa gene expression in early stages of global ischemia. Furthermore, increase in the level of mRNA Vegfa in the hippocampus (24 h after occlusion) perhaps reflects neuroprotective properties of this drug.
Subject(s)
Adrenocorticotropic Hormone/analogs & derivatives , Brain Ischemia/metabolism , Brain/metabolism , Gene Expression Regulation/drug effects , Nerve Tissue Proteins/biosynthesis , Neuroprotective Agents/pharmacology , Oligopeptides/pharmacology , Peptide Fragments/pharmacology , Proline/analogs & derivatives , Vascular Endothelial Growth Factor A/biosynthesis , Adrenocorticotropic Hormone/pharmacology , Animals , Brain/pathology , Brain Ischemia/pathology , Male , Proline/pharmacology , Rats , Rats, WistarABSTRACT
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.
Subject(s)
Factor V/genetics , Membrane Glycoproteins/genetics , Peptidyl-Dipeptidase A/genetics , Polymorphism, Genetic , Prothrombin/genetics , Adult , Aged , Brain Ischemia/genetics , Female , Gene Frequency , Genetic Predisposition to Disease , Genetics, Population , Humans , Male , Middle Aged , Platelet Glycoprotein GPIb-IX Complex , Russia , Stroke/genetics , Ukraine , White People/geneticsABSTRACT
DNA polymorphism is an important component of the interindividual variation in reactions of patients to the same drugs. In this work, evaluation of the association between polymorphisms in 106 genes involved in key processes of cellular activity (xenobiotic metabolism, DNA repair, the cell cycle, and apoptosis), and outcomes in a cohort of Yakut ovarian cancer patients receiving cisplatin-based chemotherapy was carried out. The polymorphism in the CDKN1B gene (rs34330) was found to be associated with complete tumor response and progression-free survival. SNPs in EPXH1 gene (rs2234922 and rs2260863) were correlated with hearing impairment. A SNP in NBN gene (rs1063045) was associated with severe emesis.
Subject(s)
Cisplatin/administration & dosage , Cyclin-Dependent Kinase Inhibitor p27/genetics , Genetic Association Studies , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/genetics , Apoptosis/genetics , Cell Cycle/genetics , DNA Repair/genetics , Disease-Free Survival , Female , Genetic Predisposition to Disease , Humans , Neoplasm Staging , Ovarian Neoplasms/pathology , Pharmacogenetics , Polymorphism, Single Nucleotide , Russia , Xenobiotics/metabolismABSTRACT
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.
Subject(s)
Hippocampus/metabolism , Homeostasis/drug effects , Oligopeptides/administration & dosage , Transcriptome/genetics , Animals , Cell Line , Cell Membrane/drug effects , Hippocampus/cytology , Hippocampus/drug effects , Membrane Proteins/metabolism , Oligonucleotide Array Sequence Analysis/methods , RNA, Messenger/drug effects , RNA, Messenger/metabolism , Rats , Transcriptome/drug effectsABSTRACT
Polymorphism ofglutathione-S-transferase (GSTA1, GSTM1, GSTM3, GSTP1, and GSTT1) and DNA repair (ERCC1, ERCC2, and XRCC1) genes in samples of ovarian cancer patients and healthy women of the Russian ethnic group was studied. A trend in the allele frequency variation of ERCC2 gene single nucleotide polymorphism (rs13181, A > C) was revealed. The A allele frequency was higher in the sample of patients (60,6% versus 52,9%, P = 0.058).
Subject(s)
DNA Repair Enzymes/genetics , Ovarian Neoplasms/genetics , Xeroderma Pigmentosum Group D Protein/genetics , Female , Gene Frequency , Genetic Association Studies , Genetic Predisposition to Disease , Genotype , Glutathione Transferase/genetics , Humans , Polymorphism, Single Nucleotide , Risk Factors , RussiaABSTRACT
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.
Subject(s)
Cardiovascular Diseases/genetics , Ischemia/genetics , Oxygenases/genetics , Stroke/genetics , Female , Genetic Association Studies , Humans , Multigene Family/genetics , Polymorphism, Single Nucleotide , Risk FactorsABSTRACT
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.
Subject(s)
Polymorphism, Genetic , Stroke/genetics , Adult , Aged , Aged, 80 and over , Aryldialkylphosphatase/genetics , Cyclic Nucleotide Phosphodiesterases, Type 3/genetics , Cyclic Nucleotide Phosphodiesterases, Type 4 , Cytochrome P-450 CYP11B2/genetics , DNA Mutational Analysis , Factor XII/genetics , Female , Genetic Markers , Genome-Wide Association Study , Humans , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Male , Membrane Glycoproteins/genetics , Middle Aged , Nitric Oxide Synthase Type II/genetics , Platelet Glycoprotein GPIb-IX Complex , Russia/epidemiology , Stroke/epidemiologyABSTRACT
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.
Subject(s)
Centromere/genetics , Chromosomes, Human, Pair 7/genetics , Stroke/ethnology , Stroke/genetics , Aged , Aged, 80 and over , DNA/genetics , Embolism/complications , Female , Genetic Markers , Heart Diseases/complications , Humans , Male , Middle Aged , Oligonucleotide Array Sequence Analysis , White People/geneticsABSTRACT
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.
Subject(s)
Brain Ischemia/genetics , Genetic Predisposition to Disease , Hemostasis/genetics , Polymorphism, Single Nucleotide , Renin-Angiotensin System/genetics , Stroke/genetics , Aged , Alleles , Brain Ischemia/epidemiology , Female , Gene Frequency/genetics , Humans , Male , Middle Aged , Russia/epidemiology , Stroke/epidemiologyABSTRACT
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).
Subject(s)
Fibroblast Growth Factors/genetics , Parkinson Disease/genetics , Polymorphism, Single Nucleotide/genetics , 3' Untranslated Regions , Gene Expression , Gene Frequency , Genetic Association Studies , Humans , Linkage Disequilibrium , Russia , White People , alpha-Synuclein/metabolismABSTRACT
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.
Subject(s)
Cyclic Nucleotide Phosphodiesterases, Type 3/genetics , Stroke/genetics , Adult , Cyclic Nucleotide Phosphodiesterases, Type 4 , Female , Genetic Association Studies , Haplotypes , Humans , Male , Middle Aged , Moldova , Polymorphism, Single Nucleotide/genetics , RussiaABSTRACT
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.
Subject(s)
Anti-Anxiety Agents/pharmacology , Antiviral Agents/pharmacology , Chemokines/genetics , Cytokines/genetics , Gene Expression/drug effects , Immunologic Factors/pharmacology , Nootropic Agents/pharmacology , Oligopeptides/pharmacology , Animals , Anti-Anxiety Agents/chemistry , Antiviral Agents/chemistry , Immunologic Factors/chemistry , Mice , Nootropic Agents/chemistry , Oligopeptides/chemistry , RNA, Messenger/genetics , Receptors, Cytokine/genetics , Tuftsin/chemistry , Tuftsin/pharmacologyABSTRACT
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.
Subject(s)
Parkinson Disease/genetics , Wnt Proteins/genetics , Female , Genetic Association Studies , Humans , Male , Polymorphism, Single Nucleotide/genetics , Russia , Wnt3 ProteinABSTRACT
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.
Subject(s)
Gene Expression , Glycogen Synthase Kinase 3/genetics , Parkinson Disease/blood , Parkinson Disease/diagnosis , Adult , Aged , Early Diagnosis , Female , Genetic Markers , Glycogen Synthase Kinase 3 beta , Humans , Male , Middle Aged , Parkinson Disease/geneticsABSTRACT
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.
Subject(s)
5-Lipoxygenase-Activating Proteins/genetics , Genetic Association Studies , Polymorphism, Single Nucleotide , Stroke/genetics , Adult , Aged , Alleles , Case-Control Studies , Female , Genetic Predisposition to Disease , Genotype , Humans , Male , Middle Aged , Risk Factors , Russia/epidemiology , Stroke/epidemiologyABSTRACT
The CYP2E1 gene polymorphism has been studied in Yakut women with ovarian cancer and without cancer. The two groups have been found to substantially differ in the frequency of the CYP2E1* 1D allele (with a 96-bp insertion in the promoter region of the gene): it is more frequent in healthy women (16.3 versus 7.4%, P = 0.007).
Subject(s)
Alleles , Cytochrome P-450 CYP2E1/genetics , Mutagenesis, Insertional , Ovarian Neoplasms/genetics , Polymorphism, Genetic , Promoter Regions, Genetic/genetics , Female , Humans , Ovarian Neoplasms/epidemiology , Ovarian Neoplasms/ethnology , Risk Factors , Siberia/epidemiology , Siberia/ethnologyABSTRACT
Neurotrophins regulate key function of nervous tissue cells. Analysis of neurotrophins mRNA expression is an appropriate tool to assess therapeutic efficiency of the anti-stroke drugs. We have analyzed the effect of synthetic peptide semax and its C-terminal Pro-Gly-Pro tripeptide upon mRNAs expression of neurotrophins Ngf, Bdrf, Nt-3 and their receptors TrkA, TrkB, TrkC, p75 in rat frontal lobes, hippocampus and cerebellum after bilateral common carotid artery occlusion. The animals were decapitated 30 min, 1, 2, 4, 8, 12, 24 h after the operation. The mRNA expression of neurotrophins and their receptors was assessed by relative quantification using real-time RT-PCR. Our showed that ischemia causes a significant decrease in gene expression in the hippocampus. Semax and PGP affected the expression of neurotrophins and their receptors predominantly in the frontal cortex and hippocampus of the ischemized animals. In the frontal cortex, Semax treatment resulted in a decrease of mRNA level of receptors, while PGP treatment increased the level of these mRNA. Maximal neuroprotective effect of both peptides has been observed in the hippocampus 12 h after occlusion. A decrease of gene expression of neurotrophins and their receptors caused by the occlusion was overcome by Semax and PGP. These results clarify the semax mechanism of and present certain features of mRNA's expression of neurotrophins and their receptors in experimental conditions.