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68 Publications visible to you, out of a total of 68
Association of schizophrenia with variants of genes that encode transcription factors

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Transcription factors c-Fos, c-Jun, and Ier5 are important regulators of neuronal plasticity and immune response. In the present work, several single nucleotide polymorphisms of the genes that encode … c-Fos-,c-Jun-, and Ier5 (FOS, JUN, and IER5, respectively) were investigated for potential association with schizophrenia. DNA samples obtained from patients with schizophrenia and healthy individuals were genotyped by polymerase chain reaction with allele-specific primers. It was shown that FOS rs1063169, FOS rs7101, JUN rs11688, and IER5 rs6425663 polymorphisms were associated with schizophrenia. In particular, the risk of schizophrenia was decreased in carriers of the minor alleles FOS rs1063169*T, JUN rs11688*A, and IER5 rs6425663*T, but increased in carriers of the FOS rs7101*T minor variant, especially in homozygotes.

Authors: A. S. Boyajyan, S. A. Atshemyan, R. V. Zakharyan

Date Published: 11th Dec 2015

Publication Type: Journal

Risk and Protective Effects of the Complexin-2 Gene and Gene-Environment Interactions in Schizophrenia

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Schizophrenia (SCZ) is a multifactorial chronic and disabling mental disease. The specific genetic variants contributing to disease complex phenotype are largely unknown. Growing amount of evidence … suggested that aberrant synaptic connectivity contributes to SCZ pathogenesis. From this point of view, complexin-2, a presynaptic regulatory protein, represents here a special interest, since it has been recently shown that genetic variants of the CPLX2 gene may affect current cognitive performance in patients with SCZ. A specific objective of this study was to evaluate if tagging single nucleotide polymorphisms (rs3892909, rs1366116) of gene encoding complexin-2 protein (CPLX2) linked to SCZ and to examine their relationships with complexin-2 blood levels. DNA samples of 260 patients with SCZ and 260 sex- and age-matched healthy controls were genotyped for the selected polymorphisms by application of polymerase chain reaction with sequence-specific primers, and concentration of complexin-2 in the blood plasma was determined using the enzymelinked immunosorbent assay. All study subjects were unrelated Armenians. According to the obtained results, in the patients group both the frequency distribution and carriage rate of the CPLX2 rs1366116*T minor allele were higher than in controls. On the contrary, the frequency distribution and carriage rate of the CPLX2 rs3892909*T minor allele in control group were higher than in patients. This data suggested that the presence of the CPLX2 rs1366116*T allele increases susceptibility to SCZ, whereas the rs3892909*T allele of the CPLX2 decreases the risk of SCZ. Furthermore, we found that CPLX2 rs1366116*T heterozygosity is associated with earlier disease onset. No difference between complexin-2 plasma levels in patients and controls and no significant interaction between complexin-2 plasma levels and CPLX2 genotypes in both groups were observed. In summary, we concluded that the CPLX2 rs1366116*T variant represents a risk factor of SCZ, and that, at the same time, the CPLX2 rs3892909*T variant is protective against SCZ.

Authors: Roksana Zakharyan, Sofi Atshemyan, Anna Boyajyan

Date Published: 24th Oct 2014

Publication Type: Journal

Nerve growth factor and its receptor in schizophrenia

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Promising studies suggest that defects in synaptic plasticity detected in schizophrenia may be linked to neurodevelopmental and neurodegenerative abnormalities and contribute to disease-associated … cognitive impairment. We aimed to clarify the role of the synaptic plasticity regulatory proteins, nerve growth factor (NGF) and its receptor (NGFR) in the pathogenesis of schizophrenia by comparative analysis of their blood levels and functional single nucleotide polymorphisms (SNPs) in genes encoding these proteins (NGF and NGFR) in schizophrenia-affected and healthy subjects. Relationships between the selected SNPs' genotypes and NGF and NGFR plasma levels were also assessed. Our results demonstrated a positive association between schizophrenia and the NGF rs6330 as well as the NGFR rs11466155 and rs2072446 SNPs. Also, a negative association between this disorder and NGF rs4839435 as well as NGFR rs734194 was found. In both, haloperidol-treated and antipsychotic-free patients decreased blood levels of the NGF and NGFR were found, and a positive interrelation between rs6330 and rs2072446 carriage and decreased NGF and NGFR levels, respectively, was revealed. In conclusion, our results demonstrate association of schizophrenia with the rs6330, rs4839435 and rs734194, rs11466155, rs2072446 as well as with the decreased blood levels of corresponding proteins. Our findings indicate the implication of alterations in NGFR and NGFR genes in schizophrenia, particularly, in defects of synaptic plasticity. Furthermore, the data obtained suggests that at least in Armenian population the NGF rs6330*T and NGFR rs11466155*T, rs2072446*T alleles might be nominated as risk factors, whereas the NGF rs4839435*A and NGFR rs734194*G alleles might be protective against developing schizophrenia.

Authors: Roksana Zakharyan, Sofi Atshemyan, Anaida Gevorgyan, Anna Boyajyan

Date Published: 1st Jun 2014

Publication Type: Journal

Inflammatory cytokine network in schizophrenia

Abstract (Expand)

Objectives: The purpose of this review is to analyse, sum up and discuss the available literature on the role of inflammation and inflammatory cytokines in the pathogenesis of schizophrenia. Methods: …: An electronic literature search of peer-reviewed English language articles using Pubmed was undertaken. These articles together with those published by us provided the background for the present review. Results: An overview of the available literature on this issue clearly demonstrated the alterations in mRNA and protein expression levels of several proinflammatory and chemotactic cytokines in patients with schizophrenia. Importantly, some of these changes are genetically determined. It was noteworthy that, depending on the study population, some variations of the data obtained are detected. Conclusions: Altered inflammatory cytokine production, both genetically and environmentally determined, is implicated in schizophrenia and contributes to disease-associated low-grade systemic inflammation. Proinflammatory and chemotactic cytokines and their receptors may represent additional therapeutic targets for treatment of schizophrenia.

Authors: Roksana Zakharyan, Anna Boyajyan

Date Published: 16th Sep 2013

Publication Type: Journal

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

Abstract (Expand)

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

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