CCL5/RANTES Gene Polymorphisms in Slavonic Patients with Myocardial Infarction

Coronary artery inflammation is a critical process in the pathogenesis of myocardial infarction (MI). The chemokine CCL5/RANTES (regulated upon activation, normal T cells expressed and secreted) is expressed in advanced atherosclerotic lesions. Functional polymorphisms of the RANTES gene can, therefore, be involved in the pathogenesis of coronary artery disease. We examined the association of polymorphisms in the RANTES gene with myocardial infarction in Slavonic populations of Czech and Russian origin. A total of 467 post-MI patients and 337 control subjects were genotyped for RANTES promoter G-403A (rs2107538) and intron 1.1 T/C (rs2280789) variants by PCR-SSP. Both RANTES genotypes and allele frequencies did not differ between case and control groups. Haplotype-based analysis also failed to reveal an association between MI and investigated markers. Strong linkage disequilibrium was detected between particular RANTES alleles. The data do not support an association between RANTES G-403A polymorphism and MI, as reported previously

Paucity and preferential suppression of transgenes in late replication domains of the D. melanogaster genome

<p>Abstract</p> <p>Background</p> <p>Eukaryotic genomes are organized in extended domains with distinct features intimately linking genome structure, replication pattern and chromatin state. Recently we identified a set of long late replicating euchromatic regions that are underreplicated in salivary gland polytene chromosomes of <it>D. melanogaster</it>.</p> <p>Results</p> <p>Here we demonstrate that these underreplicated regions (URs) have a low density of <it>P</it>-<it>element </it>and <it>piggyBac </it>insertions compared to the genome average or neighboring regions. In contrast, <it>Minos</it>-based transposons show no paucity in URs but have a strong bias to testis-specific genes. We estimated the suppression level in 2,852 stocks carrying a single <it>P</it>-<it>element </it>by analysis of eye color determined by the mini-<it>white </it>marker gene and demonstrate that the proportion of suppressed transgenes in URs is more than three times higher than in the flanking regions or the genomic average. The suppressed transgenes reside in intergenic, genic or promoter regions of the annotated genes. We speculate that the low insertion frequency of <it>P-elemen</it>ts and <it>piggyBac</it>s in URs partially results from suppression of transgenes that potentially could prevent identification of transgenes due to complete suppression of the marker gene. In a similar manner, the proportion of suppressed transgenes is higher in loci replicating late or very late in Kc cells and these loci have a lower density of <it>P-elements </it>and <it>piggyBac </it>insertions. In transgenes with two marker genes suppression of mini-<it>white </it>gene in eye coincides with suppression of <it>yellow </it>gene in bristles.</p> <p>Conclusions</p> <p>Our results suggest that the late replication domains have a high inactivation potential apparently linked to the silenced or closed chromatin state in these regions, and that such inactivation potential is largely maintained in different tissues.</p

Biological Determinants of Hostility

Our aim was to study the association of hostility with the DRD4, DAT, MAOA genes in an open male population of 25–64 years old. A representative sample of men aged 25–64 years (n = 657 men, average age 44.3 ± 0.4 years) was examined in 1994–1995 and 45–64 years old (n = 781 men, average age - 56.48 ± 0.2 years) in 2003–2005 using the methods proposed by the WHO international program “MONICA-psychosocial” and “HAPIEE”. All respondents completed the hostility questionnaire on their own. Genotyping of the DRD4, DAT and MAOA gene polymorphisms was carried out. It was established that the level of hostility in the male population was 76.9% in the group of 25–64 years old and 60.3% in the group of 45–64 years old. Genotypes 4/6, 4/7 of the DRD4 gene are reliably associated with a high level of hostility; the genotype 4/4 of the DRD4 gene is associated with an average and lower level of hostility. There was no association of individual genotypes and VNTR alleles of DAT gene polymorphism with different levels of hostility. It was found that among individuals with low-active alleles of the MAOA-L gene (alleles 2 and 3), a high level of hostility was more common - 50.9%. The results of constructing a logistic regression model showed that the presence of low-active alleles (2; 3) of the MAOA gene increases the likelihood of hostility OR = 2.103 (95% CI 1.137–3.889, p = 0.018). Based on the received data we can assume that the long alleles of the DRD4 gene and the low-level allele of the MAOA-L gene are associated with hostility

Biological Determinants of Sleep Disorders

The purpose of the study is to research the effect of polymorphism of genes such as CLOCK, ARNTL, PER2, NPAS2, DRD4, DAT, TNF-α, and NPSR1 on sleep disorders in an open population of 25–64-year-old men. We conducted screening studies of representative samples of men aged 25–64 years. The general examination was carried out according to the standard methods included in the WHO MONICA-Psychosocial Program (MOPSY). Carriers of the C/T genotype of the CLOCK gene more often than others reported having “satisfactory” or “poor” sleep. Carriers of the C/T genotype of the ARNTL gene were more likely to experience anxiety dreams, and they woke up exhausted. Carriers of the A/A genotype of the PER2 gene were more likely to wake up two or more times per night, a total of four to seven times per week. In the population, C/T and T/T genotypes of the NPAS2 gene were significantly more common in individuals with 7-hour sleep. Genotype 4/6 of the DRD4 gene and genotype 9/9 of the DAT gene were significantly associated with sleep disturbances. Carriers of the heterozygous A/G genotype of the TNF-α-308 gene, compared with carriers of all other genotypes, more often rated sleep as “satisfactory” (30%) than “good.

Association of Personal Anxiety with Dopamine Receptor D4 (DRD4), DAT Genes Polymorphism

Modern studies in the world have attached high priority to the role of genetics in human psychosocial stress. People who have strong biochemical responses to stress are more inclined to develop acute and posttraumatic stress disorders. Why do such unusually strong biological reactions occur in certain people? Psychogenetics focuses on many aspects: personality traits that can affect human behavior directly. Their individual variability has been found to be a genetic trait. At present we already know a number of genes, certain allelic variants and genotypes associated with some neuropsychological characters. Among these are genes encoding intracellular and plasma protein neurotransmitter transporters and their receptors; to date, there are only several dozen genes. Of particular interest are dopaminergic system genes. However, information about the polymorphism of known genes associated with personality traits is quite limited and contradictory for open population. Under these circumstances, the chapter is devoted to the association of polymorphisms of candidate genes of the dopaminergic system with anxiety in the open population

Temperature studies of Raman spectra in MnBi2Te4 and MnSb2Te4 magnetic topological insulators

Raman spectra of magnetic topological crystalline insulators in a wide temperature range including the magnetic ordering region are studied in detail. The anharmonicity parameters and Grüneisen mode parameters of Raman-active phonons in the studied crystals have been determined. It has been shown that the temperature dependence of the frequency of the (~48 cm–1) phonon in MnBi2Te4 coincides within ±0.1 cm–1 with the standard anharmonic model disregarding the spin–phonon coupling. The polarization dependences of Raman spectra in the MnSb2Te4 crystals indicate that Sb and Mn atoms are strongly mixed in them unlike the isostructural MnBi2Te4 crystals.This work was supported by the Azerbaijan Ministry of Science and Education (program “Development of the Preparation Technology of Multifunctional Convertors Based on Nanostructures”). E.V.C. acknowledges the s-upport of St. Petersburg State University (project no. 94031444).Peer reviewe

Features of genetic manifestations in patients with abdominal obesity during atrial fibrillation in combination with arterial hypertension

Aim. To study the significance of the rs1378942 polymorphisms of the CSK gene and rs2200733 (chromosome 4q25) in the progression of AF in men with AH and AO. Materials and methods. In an observational cohort study, 116 men aged 4565 years were followed. Of these, 57 patients with AF, AH and AO and a control group including 59 patients with AF, AH and without AO. Testing of polymorphism rs1378942 of the CSK gene and rs2200733 of chromosome 4q25 using polymerase chain reaction with restriction fragment length polymorphism. All statistical calculations were performed using the Rstudio program (version 0.99.879 20092016 RStudio, Inc., USA). Results. The average age of all studied patients was 53.37.1 years. When dividing patients with AF and AH into groups based on the presence/absence of AO, it turned out that in the subgroups of carriers of different genotypes of the rs1378942 polymorphism of the CSK gene there are significant differences in BMI: in the group with BMI, there is an increase in the indicator in the series of CC, AC, AA genotypes. The highest BMI value in carriers of the CC genotype (p0.03) was in the group with AO. In the subgroups of carriers of different rs2200733 genotypes of chromosome 4q25, CC has the highest BMI (p0.05). It was proved that in the group with AO, the progression of AF occurred 2.57 times more often than in the group without AO (p0.003). Conclusion. In men with AF and AH, single nucleotide polymorphisms rs1378942 of the CSK gene and rs2200733 of chromosome 4q25 are associated with BMI. The heterozygous genotype AC rs1378942 in the CSK gene is significantly more common in patients, regardless of the presence of AO. In the group with AO, the progression of AF occurred 2.57 times more often than in the group without AO

Clinical aspects of TP53 gene inactivation in diffuse large B-cell lymphoma

Abstract Background The knowledge about specific mechanisms generating TP53 dysfunction in diffuse large B-cell lymphoma is limited. The aim of the current study was to comprehensively explore TP53 gene variability resulting from somatic mutations, promoter methylation, and allelic imbalance in tumorous tissue of diffuse large B-cell lymphoma (DLBCL). Methods DNA samples from 74 patients with DLBCL were used. Genomic DNA was isolated from paraffin blocks of lymph nodes or from extranodal biopsies of tumors by the phenol–chloroform extraction method with guanidine. Analysis of coding sequences of the TP53 gene was based on Sanger’s direct sequencing method. The methylation status of the TP53 promoter was analyzed using by methylation-specific PCR on bisulfite-converted DNA. Assessment of the detected mutations was carried out in the IARC TP53 Database and the TP53 UMD mutation database of human cancer. Results The mutations in regions coding for the DNA-binding domain were prevalent (95%). In the analyzed sample of patients, codons 275, 155, 272, and 212 were hotspots of mutations in the TP53 gene. In addition, functionally significant intron mutations (IVS6-36G > C and IVS5 + 43G > T) were detected. Instances of TP53 promoter methylation were observed only in a few samples of diffuse large B-cell lymphoma tissue. Furthermore, loss of heterozygosity was revealed only in the subgroup of patients with altered status of the gene (mutations were detected in five patients and promoter methylation in one case). Conclusions Thus, the results suggest that there are two sequential events in the formation of diffuse large B-cell lymphoma in at least some cases. The first event is mutation or methylation of the TP53 promoter, leading to appearance of a cell with increased risk of malignant transformation. The second event is the loss of an intact allele of the gene; this change is necessary for tumorigenesis. We identified TP53 mutation patterns in a Russian cohort of patients with de novo DLBCL who were treated with R-CHOP and R-CHOP-like regimens and confirmed that TP53 mutation status is a valuable prognostic biomarker

Association of the genetic markers for myocardial infarction with sudden cardiac death

Objective: Investigate the association of rs17465637 gene MIAF3 (1q41), rs1376251 gene TAS2R50 (12p13), rs4804611 gene ZNF627 (19p13), rs619203 gene ROS1 (6q22), rs1333049 (9p21), rs10757278 (9p21), rs2549513 (16q23), rs499818 (6p24) associated with myocardial infarction available from the international genome-wide studies with sudden cardiac death (SCD) in a case–control study. Methods: A sample of SCD cases (n = 285) was formed using the WHO criteria; the control sample (n = 421) was selected according to sex and age. DNA was isolated by phenol–chloroform extraction from the myocardial tissue of SCD cases and blood of control cases. The groups were genotyped for the selected SNPs by real-time PCR using TaqMan probes (Applied Biosystems, United States). Results: No statistically significant differences in the genotype and allelic frequencies of studied single nucleotide polymorphisms between sudden cardiac death cases and control were detectable in general group. By separating the groups of sex and age differences in the genotype frequencies of rs1333049, rs10757278 and rs499818 are statistical significance. Genotypes CC of rs1333049 and GG of rs10757278 are associated with an increased sudden cardiac death risk in men (p = 0.019, OR = 1.7, 95% CI 1.1–2.8; p = 0.011, OR = 1.8, 95% CI 1.2–2.8, respectively). Genotype AG of rs499818 is associated with an increased sudden cardiac death risk in the women over 50 years old (p = 0.009, OR = 2.4, 95% CI 1.3–4.6). Conclusion: Polymorphisms rs1333049 and rs10757278 are associated with SCD in men and rs499818 in the women aged over 50 years