Association between ТР53, MDM2 and NQO1 gene polymorphisms and viral load among women with human papillomavirus

The risk of cervical cancer is caused by persistent human papillomavirus (HPV) infection. Cervical cancer is the most frequent cancer among women. Our purpose was to investigate the association between TP53 215C>G (Pro72Arg), MDM2 -410T>G, and NQO1 609C>T gene polymorphisms with a high HPV load and the influence of gene-gene interactions on prolonged HPV infection. Eighty-nine women with a high HPV viral load and 114 healthy women were involved in a case–control study. Genotyping for TP53 215C>G (Pro72Arg) and MDM2 -410T>G SNPs was carried out by allele-specific PCR and genotyping for NQO1 609C>T was performed by a TaqMan assay. Quantitative analysis of HPV DNA was performed by AmpliSens® HPV HCR screen-titer-FRT test system. Gene-gene interactions were analyzed using the multifactor dimensionality reduction (MDR) method. The study of separate SNPs of MDM2 -410T>G and NQO1 609C>T genes did not reveal any statistically significant difference in genotype and allele frequencies among women within the two groups. The frequency of the 215G (72Arg) allele and 215GG (72Arg/Arg) genotype of the TP53 gene was significantly higher in the case group than in the control group (OR = 1.74, 95 % CI = 1.10–2.73; p = 0.02 and OR = 1.97, 95 % CI = 1.13–3.46; p = 0.04, respectively). MDR analysis showed the significance of intergenic interactions of the three studied loci TP53 (rs1042522) – MDM2 (rs2279744) – NQO1 (rs1800566) for the formation of a high HPV load (OR = 3.05, 95 % CI = 1.73–5.46; p = 0.0001)

Association between mitochondrial DNA copy number and high viral load in women with high-risk human papillomavirus

The infection that most often leads to cervical cancer is human papillomavirus (HPV) infection. A sign that the HPV infection might develop into cancer is mitochondrial dysfunction and DNA damage. Increased mitochondrial DNA copy number (mtCN) has been associated with cervical neoplasm as a compensatory mechanism for mitochondrial dysfunctio

Beam heat load and pressure rise in a cold vacuum chamber

The beam heat load and the pressure in the vacuum chamber of the cold bore superconducting undulator installed at ANKA (ANgstrom source KArlsruhe) have been monitored for almost two years. Possible sources of the observed heat load could be synchrotron radiation from upstream magnets, image currents, electron and ion bombardment. In this paper, the various possible contributions to the heat load are discussed and compared with experimental results. The dynamic pressure increases nonlinearly with the average beam current. The current where it assumes a maximum varies both with the bunch intensity and with the initial vacuum pressure. A correlation between the heat load and the dynamic pressure has been observed. This study suggests that electron bombardment could explain the beam heat load and pressure rise observed for a bunch length of 10 mm

Beam heat load and pressure rise in a could vacuum chamber

The beam heat load and the pressure in the vacuum chamber of the cold bore superconducting undulator installed at ANKA (ANgstrom source KArlsruhe) have been monitored for almost two years. Possible sources of the observed heat load could be synchrotron radiation from upstream magnets, image currents, electron and ion bombardment. In this paper, the various possible contributions to the heat load are discussed and compared with experimental results. The dynamic pressure increases nonlinearly with the average beam current. The current where it assumes a maximum varies both with the bunch intensity and with the initial vacuum pressure. A correlation between the heat load and the dynamic pressure has been observed. This study suggests that electron bombardment could explain the beam heat load and pressure rise observed for a bunch length of 10 mm

MEMORY, ATTENTION, THINKING OF SCHIZOPHRENIA PATIENTS: CONNECTION WITH THE GENDER, ALCOHOL ABUSE AND POLYMORPHISM OF THE GENEM CATHEHOL-ORTHO-METHYLTRANSFERASE

Objective: analysis of the connection rs4860 Val158Met polymorphism of catechol-ortho-methyl transferase gene (COMT) with thinking, memory, attention of patients with schizophrenia taking into account comorbidity alcohol abuse and gender identity.Materials and methods: 200 patients with paranoid schizophrenia, 100 men and 100 women. Patients are distributed into subgroups by the factor of comorbidity alcohol abuse. Short-term memory, attention, thinking has been evaluated by psychometric scales. The variant of polymorphism rs4680 of gene COMT is determined by a genetic method. The subgroups were compared among themselves. The association of alcohol abuse, gender identity, genotype with features of these cognitive functions was investigated.Results: the study demonstrated a high prevalence of alcohol dependence in patients with schizophrenia. There is no clear direct effect of alcohol abuse on cognitive status. Gender peculiarities of the cognitive status of schizophrenic patients have been revealed. In men, the conjugation of the genotype Met158Met is noted with greater safety of short-term memory and attention against the background of more severe disorders of thinking in the schizophrenic type. Conclusions: the study did not confirm the significant effect of the comorbidity alcohol abuse on the cognitive processes of patients with schizophrenia. In men more severe short-term memory, attention disturbance predominate, unlike women who have a greater depth of schizophrenic thinking disturbances. The variant of Met158Met polymorphism is associated with relative safety of short-term memory and attention among men, without comorbidity alcohol abuse

Observation of Electron Clouds in the ANKA Undulator by Means of the Microwave Transmission Method

A superconducting undulator is installed in the ANKA electron storage ring. Electron clouds could potentially contribute to the heat load of this device. A microwave transmission type electron cloud diagnostic has been installed for the undulator section of the ANKA machine. We present the system layout with particular emphasis on the electron machine aspects. Hardware transfer function results and e-cloud data for different machine settings are discussed. Special care has been taken for front end filter design both on the microwave injection and pick-up side

ASSOCIATION OF MATRIX METALLOPROTEINASES GENE POLYMORPHISM WITH CLINICAL MANIFESTATIONS OF BRONCHIAL ASTHMA IN CHILDREN

In the present study, we have examined association between different polymorphic variants of metalloproteinases genes and clinical manifestations of bronchial asthma in children. We observed 103 patients including 42 children with an established diagnosis of asthma. Moreover, 61 persons were examined in the control group. All patients underwent genetic testing by allele-specific polymerase chain reaction. In particular, 320A>C polymorphic locus of ММР20 gene; Val275Ala ММР20, and -8202A>G gene ММР9 were analyzed.We have found that 30 patients (71.4% of total) had bronchial asthma of mild severity, 9 children (21.4%) exhibited moderate degree, and 3 patients (7%) had severe-grade disease. Homozygous C/C variant of the polymorphic ММР20 gene, 320A>C heterozygous variant of the ММР20 Val275Ala polymorphism, and heterozygous locus of -8202A>G ММР9 gene were found to be most frequent among the children with asthma. Generally, we have observed that the frequencies of the studied alleles and genotypes did not significantly differ berween the asthma patients and children from the control group (p < 0.05). However, in patients with GGgenotype of -8202A>G ММР9 polymorphism combined with homozygosity for the C allele of ММР20 320A>C, a more severe disease was observed, being combined with polyvalent sensitization and high total IgE levels in blood serum.In conclusion, frequencies of alleles and genotypes among patients with asthma did not show any statistically significant differences from the group of healthy children. The patients homozygous for G allele of ММР9 -8202A>G polymorphism gene and for the C allele ММР20 gene (320A>C) seem to be predisposed for a more severe clinical course of the disease

Genotypic variability of Pinus sylvestris L. on the drought-resistance attribute

There was an increase and intensification of droughts in connection with global climate change in recent decades. Not all plant organisms are able to adapt to changing environmental conditions. Therefore, the question of stressresistant (drought-resistant) genotypes selection for breeding is quite urgent. This problem also concerns forest tree plants, including Scots pine, which is one of the main foresters in the Voronezh region. The results of vegetative and generative sphere analysis of individual Scotch pine trees with the help of biotechnology, molecular-genetic and cytogenetic method are given in this study. The possibility of applying the tissue culture method in vitro for testing initial plants for stress resistance, including drought resistance, is explained by the interconnection of cells, tissues and the whole plant properties. It is shown that the cytogenetic characteristics of the seed progeny and the indicators of callusogenic reactions do not always coincide in different genotypes: in some cases energy resources are spent on ontogeny protection, while, in other cases, to reproductive function maintain. There are trees, in which the state the generative sphere in arid years is at the level of optimal years, and their callus cultures reaction remains unchanged even under simulated conditions of drought. Based on the results obtained for the selection of Scots pine drought-resistant genotypes we suggest applying a system of criteria characterizing both the ability of the vegetative sphere to survive in drought conditions on the basis of the tissue culture method in vitro (callus tissue formation speed, its viability, frequency of callusogenesis), and the state of the generative sphere with the help of cytogenetic analysis of seed progeny (frequency of mitosis pathologies, the proportion of cells with micronuclei, mitotic activity). The expediency of applying the biotechnological approach was proved by analysis of the gene expression level of stress proteins: the level of AbaH gene expression correlates greatly with the indicator of the viability of callus cultures, including ones on a nutrient medium with an additional stress agent (NaCl). Trees that can be assigned to drought-resistant ones, according to the results of the analysis, should be recommended for use in breeding

Interleukin-18 gene polymorphism in pregnancy With premature rupture of membranes: A case-control study

Background. Imbalanced pro- and anti-inflammatory systems can unfavourably condition carrying of pregnancy and provoke gestation complications, such as premature rupture of membranes.Objectives. Assessing the contribution of SNP variants -137G>C (rs187238), -607G>T (rs1946518) and -656A>C (rs5744228) of the IL-18 gene promoter to the incidence of extremely preterm premature rupture of membranes.Methods. A case-control study enrolled 120 pregnant women managed at the Perinatal Centre. The women were divided in two cohorts. The study cohort comprised 80 women with premature rupture of membranes at 22–27 weeks 6 days’ gestation hospitalised in a high-risk pregnancy unit, a control cohort consisted of 40 women with physiological pregnancy at 22–27 weeks 6 days’ gestation following outpatient counselling. The cohorts had comparable obstetric and gynaecological histories. The study exclusion criteria were: multiple gestation, foetal chromosomal anomalies, congenital foetal malformations, pregnancy due to assisted reproduction. Genotyping was performed at positions -137G>C, -607G>T and -656A>C of the IL-18 gene promoter with determining a peripheral blood IL-18 level in cohorts.Results. The premature rupture of membranes cohort had a statistically higher serum interleukin-18 concentration compared to control (p = 0.001). Genotyping of the IL-18 gene promoter revealed a statistically higher rate of homozygous -137G>C mutation (CC genotype) in the premature rupture of membranes cohort at 22–27 weeks 6 days’ term (p <0.001), 67 vs. 27% in control.Conclusion. A homozygous IL-18 -137G>C polymorphic variant associated with elevated blood IL-18 levels is statistically more common in pregnant women having premature rupture of membranes at 22–27 weeks 6 days’ gestation

Роль мутаций генов металлопротеиназ и рецептора эпителиального фактора роста в патогенезе бронхиальной астмы у детей

The pathogenesis of bronchial asthma (BA) is based on chronic allergic inflammation of bronchi, which affects not only microcirculation disorders, activation of lipid peroxidation, but also tissue remodeling. Matrix metalloproteinases (MMP) and epithelial growth factor (EGF) play a significant role in bronchial remodelling processes. This paper attempts to investigate the effect of gene mutations ММР and EGFR on the development of BA as well as evaluate the role of intergenic interaction. Methods. Polymorphic variants were studied in BA patients and control group patients by allelspecific polymerase chain reaction (using SNP-express reagent kits). 2073A>T gene EGFR, 320A>C gene MMP20, 837Т>C gene MMP20 и -8202A>G gene MMP9. Results. The analysis of the genetic study results showed statistically significant differences in the frequency of alleles and genotypes in polymorphism. 2073A>T gene EGFR among BA patients and control group children (p < 0.05). Significantly increased allel frequency is registered. 2073T gene EGFR in the group of BA patients (82.5%) compared to the control group (55.8%) (p = 0.003). In the study of genes polymorphisms of matrix metalloproteinases no statistically significant differences were revealed. However, the analysis of intergenic interaction shows that polymorphisms -8202A>G gene MMP9 and 2073A>T gene EGFR have a synergistic effect on each other, increasing the risk of developing BA in children. Conclusion. According to the results of studies it was found that the risk of BA development is significantly increased in homozygotes on T-allel polymorphic variant 2073A>T gene EGFR, with the frequency of occurrence of genotypes and alleles of this polymorphism statistically significantly different from the control group (p < 0.05).В основе патогенеза бронхиальной астмы (БА) лежит хроническое аллергическое воспаление бронхов, которое затрагивает процессы не только нарушения микроциркуляции, активации перекисного окисления липидов, но и ремоделирования тканей. Матриксные металлопротеиназы (Matrix metalloproteinases – ММР) и эпителиальный фактор роста (Epidermal Growth Factor – EGF) играют значимую роль в процессах ремоделирования бронхов. В данной работе предпринята попытка исследовать влияние мутаций генов ММР и EGFR на развитие БА, а также оценить роль межгенного взаимодействия. Материалы и методы. У больных, страдающих БА, и пациентов контрольной группы методом аллель-специфичной полимеразной цепной реакции (с использованием наборов реагентов SNP-экспресс) исследованы полиморфные варианты 2073A>T гена EGFR, 320A>C гена MMP20, 837Т>C гена MMP20 и -8202A>G гена MMP9. Результаты. По результатам анализа генетического исследования показано наличие статистически значимых отличий по частоте встречаемости аллелей и генотипов по полиморфизму 2073A>T гена EGFR среди больных БА и детей контрольной группы (р < 0,05). Зарегистрирована значимо повышенная частота аллеля 2073Т гена EGFR в группе больных БА (82,5 %) по сравнению с группой контроля (55,8 %) (р = 0,003). При исследовании полиморфизмов генов матриксных металлопротеиназ у обследованных статистически значимых различий не выявлено. Однако при анализе межгенного взаимодействия показано, что полиморфизмы -8202A>G гена MMP9 и 2073A>T гена EGFR оказывают синергичное влияние друг на друга, повышая риск развития БА у детей. Заключение. По результатам исследований установлено, что риск развития БА значительно повышен у гомозигот по Т-аллели полиморфного варианта 2073A>T гена EGFR, при этом частота встречаемости генотипов и аллелей данного полиморфизма статистически значимо отличается от таковой в группе контроля (р < 0,05)