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28 Publications visible to you, out of a total of 28
Association of Genetic Variants of Dopamine and Serotonin In Schizophrenia

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Background Several studies indicated that antipsychotic treatment response and side effect manifestation can be different due to inter-individual variability in genetic variations. Aim of the study … Here we perform a case-control study to explore a potential association between schizophrenia and variants within the antipsychotic drug molecular targets (DRD1, DRD2, DRD3, HTR2A, HTR6) and metabolizing enzymes (CYP2D6, COMT) genes in Armenian population including also analysis of their possible relationship with disease clinical symptoms. Methods A total of 18 SNPs was studied in patients with schizophrenia (n = 78) and healthy control subjects (n = 77) using MassARRAY genotyping. Results: We found that two studied genetic variants, namely DRD2 rs4436578*C and HTR2A rs6314*A are underrepresented in the group of patients compared to healthy subjects. After the correction for multiple testing, the rs4436578*C variant remained significant while the rs6314*A reported borderline significance. No significant differences in minor allele frequencies for other studied variants were identified. Also, a relationship between the genotypes and age of onset as well as disease duration has been detected. Conclusions The DRD2 rs4436578*C genetic variant might have protective role against schizophrenia, at least in Armenians.

Authors: Roksana Zakharyan, Hovsep Ghazaryan, Lenka Kocourkova, Andranik Chavushyan, Artur Mkrtchyan, Veronika Zizkova, Arsen Arakelyan, Martin Petrek

Date Published: No date defined

Publication Type: Journal

Telomere shortening in blood leukocytes of patients with posttraumatic stress disorder

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Telomeres are protective fragments on chromosome ends involved in maintaining genome stability, preventing chromosomal fusions, regulation of cell division. It was shown that telomere attrition rate … is accelerated in age-related diseases, as well as in response to physiological and psychosocial stress. The aim of this study was to evaluate relative leukocyte telomere length (LTL) in patients with post traumatic stress disorder (PTSD), as well as to investigate association of functional SNPs of telomerase TERC and TERT genes with LTL and PTSD. The relative LTL was measured by multiplex quantitative PCR method; genotyping of TERC rs12696304, TERT rs7726159 and rs2736100 was performed by PCR with sequence specific primers. Comparison of LTL in diseased and healthy subjects showed that PTSD patients had shorter average LTL than controls. Also, the frequency and the carriage rate of the TERT rs2736100*T allele was higher in PTSD patients compared to controls. Overall our results are in line with previous research in different populations. Furthermore, we have demonstrated that rs2736100 of TERT gene was significantly associated with PTSD and the minor allele of this polymorphism may be considered as a risk factor for PTSD in the Armenian population.

Authors: Diana Avetyan, Roksana Zakharyan, Martin Petrek, Arsen Arakelyan

Date Published: No date defined

Publication Type: Journal

Brain-derived neurotrophic factor blood levels are decreased in schizophrenia patients and associate with rs6265 genotypes

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Objectives: A growing number of studies implicate brain-derived neurotrophic factor (BDNF), an important promoter of synaptic transmission and neural plasticity, in the pathogenesis of schizophrenia. … However, the existing data are controversial, that may reflect population differences between studied groups. Design and methods: In the present study we performed a comparative analysis of BDNF plasma levels and its relation with rs6265 (G196A; Val66Met) polymorphism of BDNF gene (BDNF) in schizophrenia-affected and healthy subjects (controls) of the Armenian population. To check the influence of antipsychotics on BDNF plasma levels both medicated and non-medicated patients were involved in this study. Patients with paranoid form of schizophrenia chronically treated with typical antipsychotics (n=103), age- and sex-matched controls (n=105), and 25 antipsychotic-naive first-episode schizophrenia patients were involved. The levels of BDNF in the blood plasma were measured with a solid-phase enzyme-linked immunosorbent assay. Results: Decreased plasma levels of BDNF in both medicated and non-medicated schizophrenia patients compared to controls were observed. No significant difference in BDNF levels between medicated and non-medicated patients was detected. It was also detected that, compared to individuals homozygous for the standard allele (G/G) of rs6265, carriers of the rs6265 minor allele (A/G+A/A), which is significantly more frequent in schizophrenia patients than in controls, had decreased BDNF levels. Conclusions: The data obtained suggested that the pathogenesis of schizophrenia is characterized by genetically predetermined decreased blood levels of BDNF. These results indicated that genetically determined alterations of neuroimmune modulators may be among the risk factors of schizophrenia and contribute to disease-specific pathologic changes in functional activity of both the neuronal synaptic plasticity and the immune system. Keywords: Brain-derived neurotrophic factor; Plasma levels; Schizophrenia; rs6265 Polymorphism.

Authors: Roksana Zakharyan, Anna Boyajyan

Date Published: No date defined

Publication Type: Journal

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

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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: No date defined

Publication Type: Journal

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

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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: No date defined

Publication Type: Journal

Association of Bax and Bcl-2 Functional Polymorphisms and Protein Levels with Posttraumatic Stress Disorder

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Background: Posttraumatic stress disorder (PTSD) is an anxiety disease influenced by both environmental and genetic factors, which affects a patient’s quality of life and social stability. Recent studies … have shown that the pathogenesis of PTSD is associated with apoptosis; however, the molecular mechanisms that cause such damage are not well-understood. Also it is unclear whether these pathologic alterations are genetically determined or caused by other factors. The aim of this study was to investigate the genetic association of functional polymorphisms in genes coding for apoptosis-related Bcl-2 and Bax proteins with PTSD as well as proteins levels in the blood of affected subjects. Methods: The study groups consisted of 200 combat veterans with PTSD and an equal number of healthy subjects with no family- or past-history of any psychiatric disorders. Bax and Bcl-2 proteins levels in blood were measured by ELISA. DNA samples were genotyped for SNPs using PCR-SSP. Results: According to our results, PTSD patients are characterized by increased levels of apoptotic proteins and the imbalance in the Bax/Bcl-2 ratio compared to healthy subjects. Our results also demonstrate that rs956572*A minor allele of the BCL2 gene was overrepresented in patients with PTSD compared to healthy subjects. Conclusions: The results implicate Bcl-2 and Bax in pathogenesis of PTSD on genetic and protein levels, though further studies on enlarged cohort and in different populations are required.

Authors: Diana Avetyan, Arsen Arakelyan, Gohar Mkrtchyan

Date Published: No date defined

Publication Type: Journal

Genetic Polymorphisms of Nervous System Development and the Risk of Posttraumatic Stress Disorder

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Background: Posttraumatic stress disorder (PTSD) is a complex severe polygenic psychiatric disease, influenced by environmental and genetic factors. PTSD development and progression is characterized … by cognitive impairment, which may result in altered processes of nervous system development and synaptic plasticity, where a number of growth factors and their receptors were shown to play important role. Since neurotrophins play an essential role in the development of central nervous system, it is widely implicated in psychiatric disorders. The aim of this study is to investigate the potential association functional polymorphisms of genes encoding netrin G1 (NTNG1), brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and its receptor (NGFR) with PTSD. Methods: Study groups consisted of 200 combat veterans with PTSD and an equal number of controls with no family or past history of any psychiatric disorders. The DNA samples were genotyped for NTNG1 rs62811; BDNF rs6265; NGF rs6330, rs4839435; NGFR rs11466155, rs734194 SNPs using polymerase chain reaction with sequence specific primers. Results: According to the results, NGF rs6330 was overrepresented in patients with PTSD compared to controls. Furthermore, negative association for BDNF rs6265, NGF rs4839435 and NGFR rs734194 was observed in PTSD patients. Conclusions: In summary, BDNF rs6265, NGF rs6330, rs4839435 and NGFR rs734194 are implicated in PTSD in Armenian population. However, further research is required to provide the definitive evidence of selected polymorphism association with gene expression.

Authors: Diana Avetyan, Arsen Arakelyan, Gohar Mkrtchyan

Date Published: No date defined

Publication Type: Journal

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