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126 Publications visible to you, out of a total of 126
Association of C1QB gene polymorphism with schizophrenia in Armenian population

Abstract (Expand)

Background: Schizophrenia is a complex, multifactorial psychiatric disorder. Our previous findings indicated that altered functional activity of the complement system, a major mediator of the immune … response, is implicated in the pathogenesis of schizophrenia. In order to explore whether these alterations are genetically determined or not, in the present study we evaluated the possible association of complement C1Q component gene variants with susceptibility to schizophrenia in Armenian population, focusing on four frequent single nucleotide polymorphisms (SNPs) of C1QA and C1QB genes. Methods: In the present study four SNPs of the complement C1Q component genes (C1QA: rs292001, C1QB rs291982, rs631090, rs913243) were investigated in schizophrenia-affected and healthy subjects. Unrelated Caucasian individuals of Armenian nationality, 225 schizophrenic patients and the same number of age- and sex-matched healthy subjects, were genotyped. Genotyping was performed using polymerase chain reaction with sequence-specific primers (PCR-SSP) and quantitative real-time (qRT) PCR methods. Results: While there was no association between C1QA rs292001, C1QB rs913243 and rs631090 genetic variants and schizophrenia, the C1QB rs291982*G minor allele was significantly overrepresented in schizophrenic patients (G allele frequency 58%) when compared to healthy subjects (46%, OR = 1.64, p(corr) = 0.0008). Importantly, the susceptibility for schizophrenia was particularly associated with C1QB rs291982 GG genotype (OR = 2.5, p(corrected) = 9.6E-5). Conclusions: The results obtained suggest that C1QB gene may be considered as a relevant candidate gene for susceptibility to schizophrenia, and its rs291982*G minor allele might represent a risk factor for schizophrenia at least in Armenian population. Replication in other centers/populations is necessary to verify this conclusion.

Authors: Roksana Zakharyan, Aren Khoyetsyan, Arsen Arakelyan, Anna Boyajyan, Anaida Gevorgyan, Anna Stahelova, Frantisek Mrazek, Martin Petrek

Date Published: 28th Sep 2011

Publication Type: Journal

Functional characterization of the complement receptor type 1 and its circulating ligands in patients with schizophrenia

Abstract (Expand)

Background: Whereas the complement system alterations contribute to schizophrenia, complement receptors and regulators are little studied. We investigated complement receptor type 1 (CR1) expression … on blood cells, the levels of circulating immune complexes (CIC) containing ligands of CR1, C1q complement protein and fragments of C3 complement protein (C1q-CIC, C3d-CIC), and CR1 C5507G functional polymorphism in schizophrenia patients and controls. Results: We found an increased C1q-CIC level and CR1 expression on blood cells, elevated number of CR1 positive erythrocytes and reduced number of CR1 positive lymphocytes and monocytes in patients compared to controls. No difference in the levels of C3d-CIC between groups was observed. Higher CR1 expression on erythrocytes in CC genotype versus CG+GG for both groups was detected, whereas no difference was observed for other cell populations. Our results indicated that schizophrenia is associated with the increased CR1 expression and C1q-CIC level. Conclusions: Our study for the first time indicated that schizophrenia is associated with the increased CR1 expression and C1q-CIC level. Further studies in other ethnic groups are needed to replicate these findings.

Authors: Arsen Arakelyan, Roksana Zakharyan, Aren Khoyetsyan, David Poghosyan, Rouben Aroutiounian, Frantisek Mrazek, Martin Petrek, Anna Boyajyan

Date Published: 25th Aug 2011

Publication Type: Journal

Functional variants of the genes involved in neurodevelopment and susceptibility to schizophrenia in an Armenian population

Abstract (Expand)

Aberrant neurodevelopment contributes to the etiology of schizophrenia. This study aimed to investigate the potential association of netrin G1 (NTNG1) rs628117 and brain-derived neurotrophic factor … (BDNF) Val66Met (rs6265) genetic polymorphisms with susceptibility to schizophrenia. One hundred three Armenian patients with schizophrenia and 105 healthy control subjects were genotyped by polymerase chain reaction with sequence-specific primers. Whereas the NTNG1 rs628117 genotypes were equally distributed in the groups, the carriers of the less common BDNF 66Met allele were overrepresented among patients with schizophrenia when compared with healthy controls (55% vs 35%, odds ratio = 2.28, 95% confidence interval 1.14-1.98, p(corrected) = 0.006). Furthermore, the 66Met/Met genotype correlated with earlier disease onset (p = 0.024). In conclusion, our single-cohort study nominates the BDNF 66Met allele as a risk factor for schizophrenia in an Armenian population. This must be confirmed in other Armenian cohorts.

Authors: Roksana Zakharyan, Anna Boyajyan, Arsen Arakelyan, Anaida Gevorgyan, Frantisek Mrazek, Martin Petrek

Date Published: 24th May 2011

Publication Type: Journal

Phenotypic and cytologic studies of lymphoid cells and monocytes in primary culture of porcine bone marrow during infection of African swine fever virus.

Abstract (Expand)

We have modeled in vitro infection of African swine fever virus (ASFV) in primary unstimulated cells of the porcine bone marrow and have studied the phenotypical changes in the population of porcine … lymphoid cells by cytophotometry. Monocytes and large-sized lymphocytes completely vanished in 72 h of infection which is result of high sensitivity of those cells to ASFV. We describe DNA synthesis in monocytes at 24 h post infection. Cytophotometry of the uninfected cells revealed the few number of atypical lymphocytes and lymphoblasts after 72 h of cultivation; whereas in viral infected cultures, atypical cells appeared in large quantity (about 14%) with 24 h. Most of atypical lymphocytes and lymphoblasts had altered nucleus, and only a small number of atypical cells had additional nucleus. The cytophotometry of main and additional nuclei showed that DNA content didn't exceed diploid standard which indicates that the additional nuclei were consequence of fragmentation of nuclei in lymphocytes.

Authors: E M Karalova, Kh V Sargsyan, G K Hampikian, H E Voskanyan, L O Abroyan, A S Avetisyan, L A Hakobyan, H H Arzumanyan, H S Zakaryan, Zaven A Karalyan

Date Published: 24th Dec 2010

Publication Type: Journal

Genetic variants of the inflammatory C‐reactive protein and schizophrenia in Armenian population: a pilot study

Abstract (Expand)

C-reactive protein (CRP) is an inflammation marker implicated in the pathogenesis of schizophrenia. To investigate association of the CRP rs1417938, rs1800947, rs1205 variants with susceptibility to … schizophrenia 208 unrelated Armenians (103 patients and 105 healthy controls) were genotyped. In this pilot study, none of studied variants was associated with schizophrenia.

Authors: R. Zakharyan, A. Chavushyan, A. Khoyetsyan, A. Stahelova, A. Arakelyan, A. Boyajyan, F. Mrazek, M. Petrek

Date Published: 1st Sep 2010

Publication Type: Journal

The Topology of the Grapevine Genome – Admixture meets SOMmelier

Abstract (Expand)

Inferring the genetic structure of populations at the subpopulation level is crucial for understanding the evolutionary forces and demographic histories that shape genetic diversity. Among the most … widely used approaches in population genetics are methods based on admixture and structure modeling—named after the respective software tools—which have become standard due to their intuitive, interpretable outputs. In this study, we address a key methodological question: how does traditional admixture-based decomposition of genetic components in multilocus population data relate to clustering approaches that leverage machine learning, specifically Self-Organizing Maps (SOMs)? We implemented this approach through our custom SOM-based tool, SOMmelier, which enables the portrayal of genetic structure by identifying modules of co-mutated SNPs and arranging them in a topology-aware genetic landscape. In this context, topology-awareness refers to the organization of genetic modules in a two-dimensional map, where their spatial proximity reflects mutual similarity. As a case study, we applied SOMmelier to investigate the population genetics of European grapevine. Based on prior literature, we considered up to six genetic components, which formed a genetic landscape that closely mirrors the geographic expanse of the classical Mediterranean world—from Western Asia through the Caucasus to Western Europe. The resulting topology reflects the dynamic spatial and temporal nature of grapevine domestication and diffusion. SOMmelier thus represents a complementary and powerful framework for genetic data analysis. By integrating the topological structure of SNP co-variation, it offers new perspectives on population structure, evolutionary history, and trait associations in grapevine—and has broader applicability to other species and systems in population genetics.

Author: Anush Baloyan, Tomas Konecny, Emma Hovhannisyan, Nate Zadirako, Maria Nikoghosyan, Hans Binder

Date Published: No date defined

Publication Type: Unpublished

A new microtubule-stabilizing agent shows potent antiviral effects against African swine fever virus with no cytotoxicity.

Abstract (Expand)

African swine fever virus (ASFV) is the causal agent of a fatal disease of domestic swine for which no effective antiviral drugs are available. Recently, it has been shown that microtubule-targeting … agents hamper the infection cycle of different viruses. In this study, we conducted in silico screening against the colchicine binding site (CBS) of tubulin and found three new compounds with anti-ASFV activity. The most promising antiviral compound (6b) reduced ASFV replication in a dose-dependent manner (IC50 = 19.5 μM) with no cellular (CC50 > 500 μM) and animal toxicity (up to 100 mg/kg). Results also revealed that compound 6b interfered with ASFV attachment, internalization and egress, with time-of-addition assays, showing that compound 6b has higher antiviral effects when added within 2-8 h post-infection. This compound significantly inhibited viral DNA replication and disrupted viral protein synthesis. Experiments with ASFV-infected porcine macrophages disclosed that antiviral effects of the compound 6b were similar to its effects in Vero cells. Tubulin polymerization assay and confocal microscopy demonstrated that compound 6b promoted tubulin polymerization, acting as a microtubule-stabilizing, rather than a destabilizing agent in cells. In conclusion, this work emphasizes the idea that microtubules can be targets for drug development against ASFV.

Authors: Samvel Sirakanyan, Erik Arabyan, Astghik Hakobyan, Tamara Hakobyan, Garri Chilingaryan, Harutyun Sahakyan, Arsen Sargsyan, Grigor Arakelov, Karen Nazaryan, Roza Izmailyan, Liana Abroyan, Zaven Karalyan, Elina Arakelova, Elmira Hakobyan, Anush Hovakimyan, Andre Serobian, Marco Neves, João Ferreira, Fernando Ferreira, Hovakim Zakaryan

Date Published: No date defined

Publication Type: Journal

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