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28 Publications visible to you, out of a total of 28
Markers of apoptotic dysfunctions in schizophrenia

Abstract (Expand)

According to the modern concepts, alterations of apoptosis and its genetic regulation are associated with the etiopathogenesis of schizophrenia, which is observed at both the brain and peripheral blood … levels. However, studies of this phenomenon are at the initial stage, and the molecular and cellular mechanisms that underlie the anomalies of the processes of apoptotic cell death in schizophrenia are unclear. In the present study, we determined the levels of apoptotic markers, annexin A5 and H-ficolin proteins, in the sera of patients with chronic and first-episode schizophrenia and healthy subjects to test the proposed relationship between schizophrenia and the rs11575945 (−1C/T) single-nucleotide substitution (functional polymorphism) of Kozak consensus sequence in the regulatory region of the annexin A5 gene. Methods of a solid-phase enzyme-linked immunosorbent assay and polymerase chain reaction with allele-specific primers were used. It was shown that the pathogenesis of schizophrenia is characterized by an increased rate of apoptosis, which is more pronounced in the case of the first-episode neuroleptic-free patients than in the case of chronic patients that receive typical neuroleptic haloperidol. It was also shown that the rs11575945 polymorphism of the annexin A5 gene is associated with schizophrenia, and its minor allele is responsible for higher levels of the annexin A5 protein in the blood and represents one of the risk factors for the development of this disease.

Authors: A. S. Boyajyan, A. S. Chavushyan, R. V. Zakharyan, G. M. Mkrtchyan

Date Published: 15th Aug 2013

Publication Type: Journal

Interleukin‐6 promoter polymorphism and plasma levels in patients with schizophrenia

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Schizophrenia is a severe psychiatric disease with inflammatory component. Several studies indicated the increased blood levels of proinflammatory interleukin-6 cytokine in schizophrenia. However, only … limited studies explored the relationship between excess production and genetic variations of this cytokine in schizophrenia, and the results were controversial. Here, we investigated possible association of the interleukin-6 gene (IL6) rs1800795 (–174G/C) polymorphism with schizophrenia and relationship between this polymorphism and interleukin-6 protein (IL-6) blood levels. This polymorphism was found by other researchers to associate with different transcription rates and different plasma levels of IL-6. A total of 208 unrelated Armenians were genotyped by polymerase chain reaction with sequence-specific primers, and IL-6 levels were assessed by enzyme-linked immunosorbent assay. The IL6 rs1800795 alleles and genotypes in both groups were in Hardy–Weinberg (H–W) equilibrium. We found that rs1800795*C allele [38% vs 24%, P = 0.002, odds ratio (OR) = 1.95, 95% confidence interval (CI): 1.18–2.14] and its carriers (62% vs 42%, P = 0.003, OR = 2.28, 95% CI: 1.13–1.94) were more frequent in patients than in controls. IL-6 in patients was 1.5-fold higher than in controls (mean ± SD: 6.41 ± 2.47 pg/ml vs 4.15 ± 1.42 pg/ml, P = 1.9E–19). In both groups, higher IL-6 in rs1800795 GG compared to rs1800795*C allele carriers was observed (GG vs GC + CC, patients: 7.02 ± 2.83 pg/ml vs 5.39 ± 1.2 pg/ml, P = 0.0006; controls: 5.21 ± 1.17 pg/ml vs 3.38 ± 1.03 pg/ml, P = 1.6E–15). In conclusion, we report an association of IL6 rs1800795 and higher IL-6 with schizophrenia. We also conclude that IL6 rs1800795*C allele is linked to increased IL-6 blood levels and may be a risk factor for schizophrenia development at least in Armenian population.

Authors: R. Zakharyan, M. Petrek, A. Arakelyan, F. Mrazek, S. Atshemyan, A. Boyajyan

Date Published: 10th May 2012

Publication Type: Journal

Monocyte chemoattractant protein-1 in schizophrenia: -2518A/G genetic variant and protein levels in Armenian population.

Abstract (Expand)

Monocyte chemoattractant protein-1 (MCP-1) has been proposed as a contributory factor in pathophysiology of schizophrenia. The aim of the current study was to explore the possible association of the … MCP-1-2518A/G genetic polymorphism and plasma levels of MCP-1 in patients with paranoid schizophrenia. The MCP-1-2518A/G (rs1024611) polymorphism and blood levels of MCP-1 in patients with paranoid schizophrenia and healthy subjects were evaluated and compared. One hundred and three chronic patients with paranoid schizophrenia treated with neuroleptics and 105 healthy subjects were genotyped using polymerase chain reaction with sequence-specific primers (PCR-SSP) and their MCP-1 plasma levels were measured by a solid-phase enzyme-linked immunosorbent assay (ELISA). When comparisons were made between patients and controls, the frequency of the MCP-1-2518*G minor allele (35% vs 23%, p=0.009, OR=1.77, 95% CI: 1.1-2.04) and also of the MCP-1-2518*G carriers (60% vs 40%, p=0.003, OR=2.27, 95% CI: 1.13-2.01) were higher in patients. The mean value of the MCP-1 plasma level in patients with schizophrenia was significantly higher than in controls. Interestingly, the patients with the GG genotype had the highest MCP-1 level (711.4 ± 211.4 pg/ml), followed by those with the AG genotype (472.1 ± 135.8 pg/ml) and AA (372.4 ± 180.2 pg/ml) homozygotes. In conclusion, we report here the association of the -2518A/G genetic polymorphism and increased plasma levels of MCP-1 with schizophrenia and nominate -2518*G minor allele as a risk factor for schizophrenia in Armenian population.

Authors: Roksana Zakharyan, Anna Boyajyan, Arsen Arakelyan, Maya Melkumova, Frantisek Mrazek, Martin Petrek

Date Published: 17th Mar 2012

Publication Type: Journal

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

Genetic Variations Associated with Brain Disorders: Focus on Synaptic Plasticity and Apoptosis Regulatory Genes in Schizophrenia, Posttraumatic Stress Disorder and Ischemic Stroke

Abstract (Expand)

Epidemiologic, clinical and experimental data indicates that a majority of brain disorders including schizophrenia (SCZ), posttraumatic stress disorder (PTSD), and ischemic stroke (IS) are multifactorial … disorders with strong and complex genetic component. Identification of all genetic variations associated with these disorders may sufficiently contribute to understanding of their basic pathomechanisms and encourage development of new innovative approaches to their early diagnosis and treatment. The aim of this review article is to provide overview of our recent studies on evaluation of potential association of SCZ, PTSD and IS with functional single nucleotide polymorphisms (SNPs) of synaptic plasticity and apoptosis regulatory genes in Armenian population. Here, our attention was focused on genes encoding netrin G1 (NTNG1), brain-derived neurotrophic factor (BDNF), complexin-2 (CPLX2), nerve growth factor (NGF) and its receptor (NGFR), annexin family proteins - annexin A5 and annexin A11 (ANXAV, ANXA11), and B-cell lymphoma 2 (Bcl-2) family proteins - Bcl-2 proper and Bcl-2-associated X protein (BCL2, BAX). Genomic DNA samples of diseased and healthy individuals were genotyped for a number of SNPs of the mentioned genes using polymerase chain reaction with sequence-specific primers (PCR-SSP). The significance of differences in genotype and allele frequencies and minor allele carriage between patients and healthy control subjects was determined using Pearson’s Chi-square test. P-values less than 0.05 were considered statistically significant. Significant associations were found between: (1) SCZ and BDNF rs6265, CPLX2 rs1366116, rs3892909, NGF rs6330, rs4839435, NGFR rs734194, rs11466155, rs2072446, ANXAV rs11575945, BAX rs1057369 SNPs; (2) PTSD and CPLX2 rs1366116, BCL2 rs956572 SNPs; (3) IS and NTNG1 rs628117, CPLX2 rs1366116, ANXAV rs11575945 SNPs. The obtained results indicated the involvement of genetically determined alterations in synaptic plasticity and apoptosis in pathomechanisms of SCZ, PTSD and IS. The minor T allele of the CPLX2 gene rs1366116 polymorphism represents risk factor for all studied diseased conditions indicating important functional significance of this genetic variation in maintenance of synaptic plasticity. Another important conclusion of these studies is that minor alleles of some polymorphic variants of genes, encoding synaptic plasticity and apoptosis regulatory proteins, may play a protective role relative to SCZ decreasing the risk for development of this disorder. In summary, our studies emphasize the important contribution of changes in synaptic plasticity and apoptosis regulation to pathomechanisms of SCZ, PTSD, and IS as well as significant input of genetic factors to these changes.

Authors: Anna Boyajyan, Ani Stepanyan, Diana Avetyan, Hovsep Ghazaryan, Sofi Atshemyan, Roksana Zakharyan, Kristina Pirumyan, Gohar Tsakanova

Date Published: No date defined

Publication Type: Journal

Genetic polymorphisms of complement factor H in schizophrenia and ischemic stroke

Abstract (Expand)

Objectives: Alterations in the immune response are involved in pathogenesis of many neuropsychiatric disorders including schizophrenia and stroke. Our recent studies indicated alterations in the … complement system, including hyperactivation of the alternative complement pathway in patients with schizophrenia and ischemic stroke. In the present study we investigated functional single nucleotide polymorphisms (SNPs) of gene encoding factor H (CFH), a negative regulator of the alternative complement cascade, in patients with schizophrenia, ischemic stroke, and healthy controls. Methods: Genomic DNA samples of study subjects were genotyped using polymerase chain reaction with sequence specific primers. The distribution of genotypes for the selected SNP was checked for correspondence to the H–W equilibrium. In order to investigate potential association of the selected polymorphisms with schizophrenia and stroke, their allele and phenotype frequencies in patients and control subjects were compared using Pearson’s chi-squared test. Results: According to the results obtained, CFH rs424535 (2783- 526T >A) SNP was positively associated with schizophrenia, while have no association with stroke. On the contrary, CFH rs800292 (184G >A) SNP was positively associated with stroke and no association between this SNP and schizophrenia was found. Conclusions: In summary, we concluded that rs424535*A minor allele of the CFH gene may represent a risk factor for schizophrenia, and rs800912 minor allele of the CFH gene might be considered as a risk factor for ischemic stroke.

Authors: A. Boyajyan, H. Ghazaryan, A. Stepanyan, R. Zakharyan

Date Published: No date defined

Publication Type: Journal

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