Молитвенная практика в жизни студенческой молодежи Гомельского региона и Малопольского воеводства

Материалы XI Междунар. науч. конф. студентов, аспирантов и молодых ученых, Гомель, 17-18 мая 2018 г

Many obesity-associated SNPs strongly associate with DNA methylation changes at proximal promoters and enhancers

Background: The mechanisms by which genetic variants, such as single nucleotide polymorphisms (SNPs), identified in genome-wide association studies act to influence body mass remain unknown for most of these SNPs, which continue to puzzle the scientific community. Recent evidence points to the epigenetic and chromatin states of the genome as having important roles. Methods: We genotyped 355 healthy young individuals for 52 known obesity-associated SNPs and obtained DNA methylation levels in their blood using the Illumina 450 K BeadChip. Associations between alleles and methylation at proximal cytosine residues were tested using a linear model adjusted for age, sex, weight category, and a proxy for blood cell type counts. For replication in other tissues, we used two open-access datasets (skin fibroblasts, n = 62; four brain regions, n = 121-133) and an additional dataset in subcutaneous and visceral fat (n = 149). Results: We found that alleles at 28 of these obesity-associated SNPs associate with methylation levels at 107 proximal CpG sites. Out of 107 CpG sites, 38 are located in gene promoters, including genes strongly implicated in obesity (MIR148A, BDNF, PTPMT1, NR1H3, MGAT1, SCGB3A1, HOXC12, PMAIP1, PSIP1, RPS10-NUDT3, RPS10, SKOR1, MAP2K5, SIX5, AGRN, IMMP1L, ELP4, ITIH4, SEMA3G, POMC, ADCY3, SSPN, LGR4, TUFM, MIR4721, SULT1A1, SULT1A2, APOBR, CLN3, SPNS1, SH2B1, ATXN2L, and IL27). Interestingly, the associated SNPs are in known eQTLs for some of these genes. We also found that the 107 CpGs are enriched in enhancers in peripheral blood mononuclear cells. Finally, our results indicate that some of these associations are not blood-specific as we successfully replicated four associations in skin fibroblasts. Conclusions: Our results strongly suggest that many obesity-associated SNPs are associated with proximal gene regulation, which was reflected by association of obesity risk allele genotypes with differential DNA methylation. This study highlights the importance of DNA methylation and other chromatin marks as a way to understand the molecular basis of genetic variants associated with human diseases and traits

meQTL and ncRNA functional analyses of 102 GWAS-SNPs associated with depression implicate HACE1 and SHANK2 genes

Background Little is known about how genetics and epigenetics interplay in depression. Evidence suggests that genetic variants may change vulnerability to depression by modulating DNA methylation (DNAm) and non-coding RNA (ncRNA) levels. Therefore, the aim of the study was to investigate the effect of the genetic variation, previously identified in the largest genome-wide association study for depression, on proximal DNAm and ncRNA levels. Results We performed DNAm quantitative trait locus (meQTL) analysis in two independent cohorts (totaln= 435 healthy individuals), testing associations between 102 single-nucleotide polymorphisms (SNPs) and DNAm levels in whole blood. We identified and replicated 64 SNP-CpG pairs (p(adj.)< 0.05) with meQTL effect. Lower DNAm at cg02098413 located in theHACE1promoter conferred by the risk allele (C allele) at rs1933802 was associated with higher risk for depression (p(raw)= 0.014, DNAm = 2.3%). In 1202 CD14+ cells sorted from blood, DNAm at cg02088412 positively correlated withHACE1mRNA expression. Investigation in postmortem brain tissue of adults diagnosed with major depressive disorder (MDD) indicated 1% higher DNAm at cg02098413 in neurons and lowerHACE1mRNA expression in CA1 hippocampus of MDD patients compared with healthy controls (p= 0.008 and 0.012, respectively). Expression QTL analysis in blood of 74 adolescent revealed that hsa-miR-3664-5p was associated with rs7117514 (SHANK2) (p(adj.)= 0.015, mRNA difference = 5.2%). Gene ontology analysis of the miRNA target genes highlighted implication in neuronal processes. Conclusions Collectively, our findings from a multi-tissue (blood and brain) and multi-layered (genetic, epigenetic, transcriptomic) approach suggest that genetic factors may influence depression by modulating DNAm and miRNA levels. Alterations atHACE1andSHANK2loci imply potential mechanisms, such as oxidative stress in the brain, underlying depression. Our results deepened the knowledge of molecular mechanisms in depression and suggest new epigenetic targets that should be further evaluated

Determinants for a low health-related quality of life in asthmatics

People with asthma suffer from impaired health-related quality of life (HRQL), but the determinants of HRQL among asthmatics are not completely understood. The aim of this investigation was to study determinants of low HRQL in asthmatics and to study whether the determinants of HRQL differ between sexes and age groups. A cohort of three age groups in Sweden was investigated in 1990 using a questionnaire with focus on respiratory symptoms. To study quality of life, the generic instrument Gothenburg Quality of Life was used. The participants were also investigated with interviews, spirometry, and allergy testing. Asthma was diagnosed in 616 subjects. Fifty-eight per cent (n = 359) of the subjects were women; and 24% were smokers, 22% ex-smokers, and 54% were non-smokers. Women were more likely than men to report poor health-related quality of life. Respiratory symptoms severity was another independent determinant of a lower quality of life as well as airway responsiveness to irritants. Current and former smokers also reported lower quality of life. Finally, absenteeism from school and work was associated with lower quality of life. Factors such as sex, smoking habits, airway responsiveness to irritants, respiratory symptom severity, allergy, and absenteeism from school and work were associated with low HRQL in asthmatics

The Dispanins: A Novel Gene Family of Ancient Origin That Contains 14 Human Members

The Interferon induced transmembrane proteins (IFITM) are a family of transmembrane proteins that is known to inhibit cell invasion of viruses such as HIV-1 and influenza. We show that the IFITM genes are a subfamily in a larger family of transmembrane (TM) proteins that we call Dispanins, which refers to a common 2TM structure. We mined the Dispanins in 36 eukaryotic species, covering all major eukaryotic groups, and investigated their evolutionary history using Bayesian and maximum likelihood approaches to infer a phylogenetic tree. We identified ten human genes that together with the known IFITM genes form the Dispanin family. We show that the Dispanins first emerged in eukaryotes in a common ancestor of choanoflagellates and metazoa, and that the family later expanded in vertebrates where it forms four subfamilies (A–D). Interestingly, we also find that the family is found in several different phyla of bacteria and propose that it was horizontally transferred to eukaryotes from bacteria in the common ancestor of choanoflagellates and metazoa. The bacterial and eukaryotic sequences have a considerably conserved protein structure. In conclusion, we introduce a novel family, the Dispanins, together with a nomenclature based on the evolutionary origin

Albumin-Like Protein is the Major Protein Constituent of Luminal Fluid in the Human Endolymphatic Sac

The endolymphatic sac (ES) is an inner ear organ that is connected to the cochleo-vestibular system through the endolymphatic duct. The luminal fluid of the ES contains a much higher concentration of proteins than any other compartment of the inner ear. This high protein concentration likely contributes to inner ear fluid volume regulation by creating an osmotic gradient between the ES lumen and the interstitial fluid. We characterized the protein profile of the ES luminal fluid of patients (n = 11) with enlarged vestibular aqueducts (EVA) by proteomics. In addition, we investigated differences in the protein profiles between patients with recent hearing deterioration and patients without hearing deterioration. The mean total protein concentration of the luminal fluid was 554.7±94.6 mg/dl. A total of 58 out of 517 spots detected by 2-DE were analyzed by MALDI-TOF MS. The protein profile of the luminal fluid was different from the profile of plasma. Proteins identified from 29 of the spots were also present in the MARC-filtered human plasma; however, the proteins identified from the other 25 spots were not detected in the MARC-filtered human plasma. The most abundant protein in the luminal fluid was albumin-like proteins, but most of them were not detected in MARC-filtered human plasma. The concentration of albumin-like proteins was higher in samples from patients without recent hearing deterioration than in patients with recent hearing deterioration. Consequently, the protein of ES luminal fluid is likely to be originated from both the plasma and the inner ear and considering that inner ear fluid volumes increase abnormally in patients with EVA following recent hearing deterioration, it is tempting to speculate that albumin-like proteins may be involved in the regulation of inner ear fluid volume through creation of an osmotic gradient during pathological conditions such as endolymphatic hydrops

Polygenic risk for obesity and its interaction with lifestyle and sociodemographic factors in European children and adolescents

Background Childhood obesity is a complex multifaceted condition, which is influenced by genetics, environmental factors, and their interaction. However, these interactions have mainly been studied in twin studies and evidence from population-based cohorts is limited. Here, we analyze the interaction of an obesity-related genome-wide polygenic risk score (PRS) with sociodemographic and lifestyle factors for BMI and waist circumference (WC) in European children and adolescents. Methods The analyses are based on 8609 repeated observations from 3098 participants aged 2-16 years from the IDEFICS/I.Family cohort. A genome-wide polygenic risk score (PRS) was calculated using summary statistics from independent genome-wide association studies of BMI. Associations were estimated using generalized linear mixed models adjusted for sex, age, region of residence, parental education, dietary intake, relatedness, and population stratification. Results The PRS was associated with BMI (beta estimate [95% confidence interval (95%-CI)] = 0.33 [0.30, 0.37], r(2) = 0.11, p value = 7.9 x 10(-81)) and WC (beta [95%-CI] = 0.36 [0.32, 0.40], r(2) = 0.09, p value = 1.8 x 10(-71)). We observed significant interactions with demographic and lifestyle factors for BMI as well as WC. Children from Southern Europe showed increased genetic liability to obesity (BMI: beta [95%-CI] = 0.40 [0.34, 0.45]) in comparison to children from central Europe (beta [95%-CI] = 0.29 [0.23, 0.34]), p-interaction = 0.0066). Children of parents with a low level of education showed an increased genetic liability to obesity (BMI: beta [95%-CI] = 0.48 [0.38, 0.59]) in comparison to children of parents with a high level of education (beta [95%-CI] = 0.30 [0.26, 0.34]), p-interaction = 0.0012). Furthermore, the genetic liability to obesity was attenuated by a higher intake of fiber (BMI: beta [95%-CI] interaction = -0.02 [-0.04,-0.01]) and shorter screen times (beta [95%-CI] interaction = 0.02 [0.00, 0.03]). Conclusions Our results highlight that a healthy childhood environment might partly offset a genetic predisposition to obesity during childhood and adolescence.Peer reviewe