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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

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

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

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