Comorbidity of asthma and hypertension may be mediated by shared genetic dysregulation and drug side effects

Zolotareva O, Saik OV, Königs C, et al. Comorbidity of asthma and hypertension may be mediated by shared genetic dysregulation and drug side effects. Scientific Reports. 2019;9(1): 16302.Asthma and hypertension are complex diseases coinciding more frequently than expected by chance. Unraveling the mechanisms of comorbidity of asthma and hypertension is necessary for choosing the most appropriate treatment plan for patients with this comorbidity. Since both diseases have a strong genetic component in this article we aimed to find and study genes simultaneously associated with asthma and hypertension. We identified 330 shared genes and found that they form six modules on the interaction network. A strong overlap between genes associated with asthma and hypertension was found on the level of eQTL regulated genes and between targets of drugs relevant for asthma and hypertension. This suggests that the phenomenon of comorbidity of asthma and hypertension may be explained by altered genetic regulation or result from drug side effects. In this work we also demonstrate that not only drug indications but also contraindications provide an important source of molecular evidence helpful to uncover disease mechanisms. These findings give a clue to the possible mechanisms of comorbidity and highlight the direction for future research

Gene Polymorphisms of Hormonal Regulators of Metabolism in Patients with Schizophrenia with Metabolic Syndrome

Background: Metabolic syndrome (MetS) is a common complication of long-term treatment of persons with schizophrenia taking (atypical) antipsychotics. In this study, we investigated the existence of an association with polymorphisms of genes for four hormones that regulate energy metabolism. Methods: We recruited 517 clinically admitted white patients (269M/248F) with a verified diagnosis of schizophrenia (ICD-10) and with a stable physical condition. Participants were classified for having or not having MetS and genotyped for 20 single-nucleotide polymorphisms (SNPs) in the genes encoding insulin-induced gene 2 (INSIG2), ghrelin (GHRL), leptin (LEP), and leptin receptor (LEPR). Results: The 139 patients (26.9%) with MetS were significantly more likely to be women, older, and ill longer, and had a larger body mass index (BMI). Four polymorphisms (rs10490624, rs17587100, rs9308762, and rs10490816) did not meet the Hardy–Weinberg equilibrium (HWE) criterion and were excluded. Only genotypes and alleles of the rs3828942 of LEP gene (chi2 = 7.665, p = 0.022; chi2 = 5.136, p = 0.023) and the genotypes of the rs17047718 of INSIG2 gene (chi2 = 7.7, p = 0.021) had a significant association with MetS. Conclusions: The results of our study suggest that the LEP and INSIG2 genes play a certain causal role in the development of MetS in patients with schizophrenia

Genes of the Glutamatergic System and Tardive Dyskinesia in Patients with Schizophrenia

Background: Tardive dyskinesia (TD) is an extrapyramidal side effect of the long-term use of antipsychotics. In the present study, the role of glutamatergic system genes in the pathogenesis of total TD, as well as two phenotypic forms, orofacial TD and limb-truncal TD, was studied. Methods: A set of 46 SNPs of the glutamatergic system genes (GRIN2A, GRIN2B, GRIK4, GRM3, GRM7, GRM8, SLC1A2, SLC1A3, SLC17A7) was studied in a population of 704 Caucasian patients with schizophrenia. Genotyping was performed using the MassARRAY Analyzer 4 (Agena Bioscience™). Logistic regression analysis was performed to test for the association of TD with the SNPs while adjusting for confounders. Results: No statistically significant associations between the SNPs and TD were found after adjusting for multiple testing. Since three SNPs of the SLC1A2 gene demonstrated nominally significant associations, we carried out a haplotype analysis for these SNPs. This analysis identified a risk haplotype for TD comprising CAT alleles of the SLC1A2 gene SNPs rs1042113, rs10768121, and rs12361171. Nominally significant associations were identified for SLC1A3 rs2229894 and orofacial TD, as well as for GRIN2A rs7192557 and limb-truncal TD. Conclusions: Genes encoding for mGlu3, EAAT2, and EAAT1 may be involved in the development of TD in schizophrenia patients

The Gender-Specific Association of DRD2 Polymorphism with Metabolic Syndrome in Patients with Schizophrenia

BACKGROUND: Metabolic syndrome is widespread in patients with schizophrenia receiving long-term antipsychotic therapy. Dopamine D2 receptors play an important role in mediating both the therapeutic actions of antipsychotics and their side effects. The present study examined the association of two polymorphisms of the DRD2 gene with metabolic syndrome in patients with schizophrenia. METHODS: We examined 517 patients from several regions of Siberia (Russia) with a clinical diagnosis of schizophrenia. Genotyping of two single nucleotide polymorphisms rs1799732 and rs4436578 of the dopamine D2 receptor gene (DRD2) was performed in a population of 471 patients. The results were analyzed using chi-square tests. RESULTS: Functional polymorphism rs1799732 of the DRD2 gene is associated with drug-induced metabolic syndrome in women with schizophrenia. CONCLUSIONS: Our results show that the DRD2 gene may be involved in the pathogenesis of metabolic disorders in patients with schizophrenia. Further analysis of possible genetic markers will allow for personalized treatment with minimal side effects and optimal efficacy. This which seems relevant in light of the recent focus on improving the quality of life and ensuring a high level of social adaptation of patients with schizophrenia

Assessment of physicians’ and senior medical students’ knowledge in treatment of patients with community acquired pneumonia: Current results of the KNOCAP project

Introduction. Community-acquired pneumonia (CAP) remains one of the most acute problems of bronchopulmonary pathology being the 4th in the mortality structure (after cardiovascular, cerebrovascular diseases and malignant neoplasms) and the 1st among all fatalities from infectious diseases. Thanks to the scientific progress achieved in the antibiotic therapy and vaccine prophylaxis, the death toll has decreased four times compared to its rate during the “pre-antibiotic era“. However, nowadays there is a steadily increasing trend in the pneumonia mortality rate in Russia. The only possible way to increase efficacy of CAP treatment is timely initiated rational antibiotic therapy, considering the possible etiologies, risk factors and the severity of the patient’s condition. Materials and methods. The article represents the results of anonymous prospective surveys within the framework of the KNOCAP multi-centered research project aimed at accessing the knowledge on the fundamental issues in diagnosis and treatment of community-acquired pneumonia. The survey involved 222 students in their fifth- and sixth years in medical institute from Belgorod, Dnepr (Dnipro), Voronezh, Kiev (Kyiv) and Saratov and 110 physicians from Krasnodar, Saratov, Belgorod and Dnepr.Results and discussion. According to the results of the survey, such levels of correct answers were given by doctors and students, respectively: the inadmissibility of antimicrobial therapy (AMT) delay in CAP - 82% and 59%; the main criterion for withholding AMT - 56% and 37%; “sequential therapy” - 61% and 59%. At the same time, only 24% of the students and 23% of the physicians surveyed correctly reported typical mistakes in the treatment of a non-severe CAP with 50% or more accuracy; and in case of initial treatment, the number of correct responses was less than 28% for students and 45% for doctors. Conclusion. The survey showed that both senior medical students majoring in Medical Care and general practitioners had a low level of knowledge in CAP treatment. Hence, curricula need to be adjusted both in medical universities and in health institutions for practitioners in order to inform them and, thus, improve the quality of their knowledge in this field

Assessment of physicians’ and senior medical students’ knowledge in treatment of patients with community-acquired pneumonia: Current results of the KNOCAP project

Community-acquired pneumonia (CAP) remains one of the most acute problems of bronchopulmonary pathology being the 4th in the mortality structure (after cardiovascular, cerebrovascular diseases and malignant neoplasms) and the 1st among all fatalities from infectious diseases. Thanks to the scientific progress achieved in the antibiotic therapy and vaccine prophylaxis, the death toll has decreased four times compared to its rate during the “pre-antibiotic era“. However, nowadays there is a steadily increasing trend in the pneumonia mortality rate in Russia. The only possible way to increase efficacy of CAP treatment is timely initiated rational antibiotic therapy, considering the possible etiologies, risk factors and the severity of the patient’s condition

Comparative assessment of physicians’ and senior medical students’ basic knowledge in treatment of chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is one of the most common pathologies of the respira-tory system. This disease ranks third in the group of the main causes of death in the world. The effective treatment of COPD has been developed by today. However, a significant part of physicians has an insufficient amount of education in this matter

Phenological shifts of abiotic events, producers and consumers across a continent

Ongoing climate change can shift organism phenology in ways that vary depending on species, habitats and climate factors studied. To probe for large-scale patterns in associated phenological change, we use 70,709 observations from six decades of systematic monitoring across the former Union of Soviet Socialist Republics. Among 110 phenological events related to plants, birds, insects, amphibians and fungi, we find a mosaic of change, defying simple predictions of earlier springs, later autumns and stronger changes at higher latitudes and elevations. Site mean temperature emerged as a strong predictor of local phenology, but the magnitude and direction of change varied with trophic level and the relative timing of an event. Beyond temperature-associated variation, we uncover high variation among both sites and years, with some sites being characterized by disproportionately long seasons and others by short ones. Our findings emphasize concerns regarding ecosystem integrity and highlight the difficulty of predicting climate change outcomes. The authors use systematic monitoring across the former USSR to investigate phenological changes across taxa. The long-term mean temperature of a site emerged as a strong predictor of phenological change, with further imprints of trophic level, event timing, site, year and biotic interactions.Peer reviewe

Chronicles of nature calendar, a long-term and large-scale multitaxon database on phenology

We present an extensive, large-scale, long-term and multitaxon database on phenological and climatic variation, involving 506,186 observation dates acquired in 471 localities in Russian Federation, Ukraine, Uzbekistan, Belarus and Kyrgyzstan. The data cover the period 1890-2018, with 96% of the data being from 1960 onwards. The database is rich in plants, birds and climatic events, but also includes insects, amphibians, reptiles and fungi. The database includes multiple events per species, such as the onset days of leaf unfolding and leaf fall for plants, and the days for first spring and last autumn occurrences for birds. The data were acquired using standardized methods by permanent staff of national parks and nature reserves (87% of the data) and members of a phenological observation network (13% of the data). The database is valuable for exploring how species respond in their phenology to climate change. Large-scale analyses of spatial variation in phenological response can help to better predict the consequences of species and community responses to climate change.Peer reviewe

EUNIS Habitat Classification: Expert system, characteristic species combinations and distribution maps of European habitats

Aim: The EUNIS Habitat Classification is a widely used reference framework for European habitat types (habitats), but it lacks formal definitions of individual habitats that would enable their unequivocal identification. Our goal was to develop a tool for assigning vegetation‐plot records to the habitats of the EUNIS system, use it to classify a European vegetation‐plot database, and compile statistically‐derived characteristic species combinations and distribution maps for these habitats. Location: Europe. Methods: We developed the classification expert system EUNIS‐ESy, which contains definitions of individual EUNIS habitats based on their species composition and geographic location. Each habitat was formally defined as a formula in a computer language combining algebraic and set‐theoretic concepts with formal logical operators. We applied this expert system to classify 1,261,373 vegetation plots from the European Vegetation Archive (EVA) and other databases. Then we determined diagnostic, constant and dominant species for each habitat by calculating species‐to‐habitat fidelity and constancy (occurrence frequency) in the classified data set. Finally, we mapped the plot locations for each habitat. Results: Formal definitions were developed for 199 habitats at Level 3 of the EUNIS hierarchy, including 25 coastal, 18 wetland, 55 grassland, 43 shrubland, 46 forest and 12 man‐made habitats. The expert system classified 1,125,121 vegetation plots to these habitat groups and 73,188 to other habitats, while 63,064 plots remained unclassified or were classified to more than one habitat. Data on each habitat were summarized in factsheets containing habitat description, distribution map, corresponding syntaxa and characteristic species combination. Conclusions: EUNIS habitats were characterized for the first time in terms of their species composition and distribution, based on a classification of a European database of vegetation plots using the newly developed electronic expert system EUNIS‐ESy. The data provided and the expert system have considerable potential for future use in European nature conservation planning, monitoring and assessment