[Polymorphisms in Sleep and Cognitive Function Related Genes are Associated with Vehicle Crash History in Shift Working Bus Drivers].

Bus driving is a highly responsible profession. It requires constant engagement of attention and cog- nitive resources as well as vigilance and resistance to disruption of sleep- rhythms. There is ongoing research of genetic correlates of these individual characteristics. The aim of this study is to search for possible connections between single nucleotide polymorphisms and the history of road traffic accidents in professional bus driving. 299 professional drives working on rolling shifts with recorded history of traffic accidents took part in the study. Polymorphisms in circadian rhythm-, cognitive and emotional function-related genes were genotyped: CLOCK (rs 12649507), RORA (rs1159814), NPAS2 (rs4851377), NPSR1 (rs324981), PER3 (rs2640909), DRD3 (rs6280), SLC6A3 (rs6347), DBH(rs1611125). Significant associations for polymorphisms in CLOCK, NPSR1 and SLC6A3 with traffic crash parameters were found. We suppose that they are mediated by the difference in chronotype and sleep deprivation resistance for CLOCKand cognitive and emotional control for NPSRI and SLC6A3 polymorphisms.

[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.

[Genetic risk factors for recurrence-free urolithiasis in the russian population].

PURPOSE: Search for and identification of possible associations of recurrence-free urolithiasis with polymorphisms of urolithiasis candidate genes in the Russian population. MATERIALS AND METHODS: The study involved 43 patients with recurrence-free urolithiasis, 13 (30.2%) women and 30 (69.8%) of men (main group) from Central Russia, and 189 healthy adults (control group) from the same region. The mean age of the main group was 42.5+/-13 years. The venous blood samples were used for the evaluation. Real-time PCR using the "Applied Biosystems" test systems was performed to determine the spectrum and frequency of eight urolithiasis candidate genes polymorphisms: tumor necrosis factor receptor gene (TNFRSF11B (rs3134057), vitamin D receptor gene (VDR, (rs1540339), extracellular calcium-sensing receptor gene (CASR, (rs2202127), calcium release-activatedcalcium modulator 1 gene (ORAI1, rs7135617), Klotho gene (KL, rs526906), nuclear estrogen receptor alpha-subunit gene (ESR1, rs851982), tumor necrosis factor 11 gene (TNFSF11, rs9525641), and 26 gene family anionic membrane transporter gene (SLC26A6, rs2310996). Fishers angular transformation and 2 test were used for statistical analysis of the data. RESULTS: For ORAI1 gene, differences in genotype and allele frequencies in the control and main groups are significant: p=0.0001 and p=0.013, respectively. For polymorphisms of the other seven genes studied, the differences in genotype and allele frequencies are non-significant. The results indicate the presence of the association between recurrence-free urolithiasis and calcium release-activatedcalcium modulator 1 gene polymorphism (ORAI1, rs7135617), both in genotypes and alleles. CONCLUSIONS: In Russian population, genetic factors, in particular, ORAI1 (rs7135617) gene polymorphism, can play the role in the development of recurrence-free urolithiasis.

[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.

[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.

[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.

[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.

[The association of hemostasis system genes with the development of ischemic stroke in patients under the age of 50 years]. / Assotsiatsiia genov sistemy gemostaza s riskom razvitiia ishemicheskogo insul'ta u patsientov v vozraste do 50 let.

AIM: To study an influence of polymorphic variants of hemostasis system genes on the risk of ischemic stroke (IS) in patients of the Slavic population under the age of 50 years. MATERIAL AND METHODS: Ninety-two patients (19 women and 73 men), aged 18-50 years, were examined. The diagnosis of stroke was confirmed by neuroimaging (CT or MRI) in all patients. Polymorphic alleles of GP1BA, F2, F5 were studied by a real-time polymerase chain reaction using the TaqMan technology. RESULTS AND CONCLUSION: An analysis of the GP1BA -5T/C polymorphism showed that it was associated with IS in young men, lacunar stroke and stroke due to thrombosis of the brachiocephalic arteries. This association was not found in young women. The F5 G1691A polymorphism was associated with lacunar stroke. The F2 G20210A polymorphism was associated with stroke due to thrombosis of the brachiocephalic arteries.

[Associations between chronotype, road accidents and polymorphisms in genes linked with biological clock and dopaminergic system]. / Assotsiatsii khronotipa, avariinosti i polimorfizmov genov, sviazannykh s biologicheskimi chasami i dofaminergicheskoi sistemoi.

Public transport driving is a highly demanding activity requiring high skills and responsibility. Shift work, problems with regular sleep schedule negatively impact psychomotor reactions, cognitive functions and ability to react appropriately to the changing environment. For professional drivers all these factors may lead to the increased risk of a road accident. Individual differences in chronotype, cognitive and emotional control are partially genetically determined. AIM: Our study aimed to investigate the possible associations between chronotype parameters, traffic accident history and single nucleotide polymorphisms (SNPs) in a number of genes: RORA (rs1159814), CLOCK (rs12649507), PER3 (rs2640909), NPSR1 (rs324981), NPAS2 (rs4851377), DRD3 (rs6280), SLC6A3 (rs6347), DBH (rs1611125). MATERIAL AND METHODS: We have studied 303 professional bus drivers working on rolling shifts in the Moscow region who had a recorded history of road accidents. The studied group was genotyped on selected SNPs and has filled out two chronotype questionnaires: MCTQ and shortened SWPAQ (Putilov A.A, 2014). RESULTS: A mixed chronotype with high levels of morning and evening alertness prevailed in the group. A prominent social jetlag caused by shift work was found. For SNP in PER3 gene there was an association with morning activation. SNP in CLOCK gene was associated with social jetlag and the risk to cause a crash. Minor alleles of SNPs in NPSR1and SLC6A3 correlated with later chronotype and increased risk of a road accident. We suppose that these polymorphisms may be amongst the genetic factors connecting chronotype and road accident risk.

[Association of the IVS9-675C > A polymorphism of the HIF-1alpha gene with acute ischemic stroke in the Moscow population].

The IVS9-675C > A polymorphism of the HIF-1alpha gene was analyzed in patients with acute ischemic stroke and in a control group. The genotype and allele frequencies proved to significantly differ between the two groups. Allele C and genotypes containing this allele were associated with a higher risk of stroke in the Moscow population.

[Genome-wide scanning in the study of risk for cerebral stroke].

The role of genetic predisposition to the formation of most multifactorial diseases, including stroke, was demonstrated in a number of investigations. To determine the individual genetic risk of a polygenic disease, the candidate gene approach is used most often. It is based on the analysis of polymorphic variants of certain genes taking into consideration the function of their protein product. But this approach is limited by the analysis of defined genes and does not detect new groups of genes, which involved in the pathogenesis of cerebral stroke. Genome-wide association study is a wide-range analysis of whole-genome polymorphisms, which allows to compare the distribution of allele frequencies in stroke patients and healthy individuals. The use of this method for the determination of individual genetic risk of acute stroke allows to perform molecular-genetic screening of most significant markers of stroke predisposition; to determine patients with the highest risk of stroke and to perform the mass health examination with preventive therapy prescription. The genome-wide association study to determine the individual genetic risk of stroke, taking into account ethnic origin, is performed in the Russian Federation since 2008 on the basis of the Neurological clinic of the Russian State Medical University in collaboration with the Institute of Molecular Genetics, Russian Academy of Sciences.