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34 Publications visible to you, out of a total of 34
Expression of micro-RNAs miR-31, miR-146a, miR-181c and miR-155 and their target gene IL-2 are altered in schizophrenia: a case-control study

Abstract (Expand)

Background: Schizophrenia is a severe psychiatric disorder with a heterogeneous clinical phenotype. The association of interleukins and other cytokines and their receptors with schizophrenia has been … previously reported. Additionally, a number of studies have reported altered mico-RNA (miRNA) expression in schizophrenia and other psychiatric disorders. The aim of our study was to explore the possible association of miR-31, miR-146a, miR-181c and miR-155 with schizophrenia pathogenesis, as well as their link to IL2 gene expression in disease. Methods: For this case-control study, 225 patients with paranoid schizophrenia and 225 sex- and age-matched controls with no family history of schizophrenia were recruited. The expression of studied miRNAs and the IL2 gene was measured using qPCR. DNA samples of all patients and controls were genotyped for IL2 rs2069778 single nucleotide polymorphism (SNP) using PCR with sequence specific primers (PCR-SSP). Statistical analyses include the Mann-Whitney U-test and Fischer’s exact test. Results: All studied miRNAs were over-expressed in schizophrenic patients IL2 gene expression was down-regulated in schizophrenic patients. The IL2 rs2069778 SNP is not associated with schizophrenia but regulates expression of the IL2 gene. Conclusions: Over-expression of studied miRNAs and down-regulation of IL2 gene expression may be considered as genetic risk factors for chronic schizophrenia. Abnormalities in studied miRNA expressions result in the deregulation of the T-cell receptor signaling pathway in schizophrenia.

Authors: Hovsep Ghazaryan, Roksana Zakharyan, Martin Petrek, Zdenka Navratilova, Andranik Chavushyan, Eva Novosadova, Arsen Arakelyan

Date Published: 10th Dec 2019

Publication Type: Journal

Telomere shortening in blood leukocytes of patients with posttraumatic stress disorder

Abstract (Expand)

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: 21st Jan 2019

Publication Type: Journal

Involvement of polymorphisms of the nerve growth factor and its receptor encoding genes in the etiopathogenesis of ischemic stroke

Abstract (Expand)

Background: Despite the important role of the nerve growth factor in the survival and maintenance of neurons in ischemic stroke, data regarding the relationships between variations in the encoding gene … and stroke are lacking. In the present study, we evaluated the association of the functional polymorphisms in NGF (rs6330) and NGFR (rs2072446 and rs734194) genes with ischemic stroke in an Armenian population. Methods: In total, 370 unrelated individuals of Armenian nationality were enrolled in this study. Genomic DNA samples of patients and healthy controls were genotyped using polymerase chain reaction with sequence-specific primers. Results: The results obtained indicate that the minor allele of rs6330 (Pcorr = 2.4E-10) and rs2072446 (Pcorr = 0.02) are significantly overrepresented in stroke group, while the minor allele of rs734194 (Pcorr = 8.5E-10) was underrepresented in diseased subjects. Single nucleotide polymorphisms in NGF gene (rs6330) and NGFR gene (rs2072446 and rs734194) are associated with the disease. Furthermore, it was shown that the carriage of the NGF rs6330*T minor allele is associated with increased infarct volume and higher risk of recurrent stroke. Conclusions: In conclusion, our findings suggest that the NGF rs6330*T and NGFR rs2072446*T minor alleles might be nominated as a risk factor for developing ischemic stroke and NGFR rs734194*G minor allele as a protective against this disease at least in Armenian population. Keywords: Ischemic stroke, Nerve growth factor, Nerve growth factor receptor, NGF, NGFR, Single nucleotide polymorphism

Authors: Ani Stepanyan, Roksana Zakharyan, Arsen Simonyan, Gohar Tsakanova, Arsen Arakelyan

Date Published: 2nd Mar 2018

Publication Type: Journal

Characterization of BRCA1/2 mutations in patients with family history of breast cancer in Armenia.

Abstract (Expand)

Background. Breast cancer is one of the most common cancers in women worldwide. The germline mutations of the BRCA1 and BRCA2 genes are the most significant and well characterized genetic risk factors … for hereditary breast cancer. Intensive research in the last decades has demonstrated that the incidence of mutations varies widely among different populations. In this study we attempted to perform a pilot study for identification and characterization of mutations in BRCA1 and BRCA2 genes among Armenian patients with family history of breast cancer and their healthy relatives. Methods. We performed targeted exome sequencing for BRCA1 and BRCA2 genes in 6 patients and their healthy relatives. After alignment of short reads to the reference genome, germline single nucleotide variation and indel discovery was performed using GATK software. Functional implications of identified variants were assessed using ENSEMBL Variant Effect Predictor tool. Results. In total, 39 single nucleotide variations and 4 indels were identified, from which 15 SNPs and 3 indels were novel. No known pathogenic mutations were identified, but 2 SNPs causing missense amino acid mutations had significantly increased frequencies in the study group compared to the 1000 Genome populations. Conclusions. Our results demonstrate the importance of screening of BRCA1 and BRCA2 gene variants in the Armenian population in order to identity specifics of mutation spectrum and frequencies and enable accurate risk assessment of hereditary breast cancers. Keywords: BRCA1; BRCA2; breast cancer; mutation screening; targeted exome sequencing.

Authors: Sofi Atshemyan, Andranik Chavushyan, Nerses Berberian, Arthur Sahakyan, Roksana Zakharyan, Arsen Arakelyan

Date Published: 10th Jan 2017

Publication Type: Journal

Transcription Factors in Schizophrenia: A Current View of Genetic Aspects

Abstract (Expand)

Background: Schizophrenia is a polygenic mental disorder with about 80% heritability. Growing evidence indicated that synaptic dysfunctions contribute to SCZ etiopathogenesis. The context and purpose …e of the study: Transcription factors play an important role in the regulation of gene expression. Whereas expression analysis of transcription factor has been performed, studies of their genetic variants are limited. The current review article summarizes data on transcription factors early growth response 3 (EGR3), c-fos transcription (FOS), immune early response 5 (IER5), c-jun (JUN), Nk2 Homeobox 1 (NKX2-1), and transcription factor 4 (TCF4) encoding genes in schizophrenia. Results and main findings: An important role of the mentioned genes in this pathology has been identified. Conclusions: We concluded that the genetic variants of the transcription factor encodng genes might contribute to the assessment of disease susceptibility and can find potential use for the development of genetically-driven diagnostic approaches in the future.

Author: Zakharyan Roksana

Date Published: 30th Dec 2016

Publication Type: Journal

Schizophrenia-associated Risk and Protective Variants of c-Fos Encoding Gene

Abstract (Expand)

Defects in synaptic plasticity play a key role in pathophysiology of schizophrenia. Pathomechanisms responsible for synaptic plasticity alterations in schizophrenia are very complicated and not well … defined. Transcription factor c-Fos plays an important role in regulation of synaptic plasticity. In the present study we evaluated the association of rs7101 and rs1063169 single nucleotide polymorphisms (SNPs) of c-Fos encoding gene (FOS) with schizophrenia. A total of 604 DNA samples of schizophrenia-affected and healthy subjects of Armenian ancestry were genotyped using polymerase chain reaction with sequence-specific primers. Also, comparative determination of the blood levels of c-Fos protein in schizophrenia patients and controls was performed using the enzyme-linked immunosorbent assay. Potential interaction between protein level and genotypes as well as relationships between genotypes/protein level and clinical-demographic characteristics of schizophrenia patients were assessed. The results obtained demonstrated that mutant allele of FOS rs1063169 SNP is negatively associated with schizophrenia and may be nominated as a protective factor for this disorder. On the other hand, according to our results, the FOS rs7101T mutant allele is positively associated with schizophrenia and, therefore, may be considered as a risk factor for this disorder. In addition, decreased c-Fos plasma levels in schizophrenia patients compared to controls were found. In conclusion, the results of this study suggest that FOS is among the candidate genes of schizophrenia and that changes in the expression of c-Fos protein may contribute to molecular pathomechanisms of schizophrenia-related alterations in synaptic plasticity.

Authors: Anna Boyajyan, Roksana Zakharyan, Sofi Atshemyan, Andranik Chavushyan, Gohar Mkrtchyan

Date Published: 26th Jan 2016

Publication Type: Journal

No Association of the Complexin-3 Gene Polymorphism with Schizophrenia

Abstract (Expand)

Background: Schizophrenia (SCZ) is a multifactorial mental disease. Whereas complex interplay of genes and environment contributes to the SCZ, the disorder has still unclear biological background. … Growing amount of evidence showed that synaptic dysfunctions are contributed to SCZ etiopathogenesis. The context and purpose of the study: Complexin-3, a presynaptic regulatory protein, represents here a special interest. This study was aimed to investigate the potential association of SCZ with rs3743487 single nucleotide polymorphism of the complexin-3 protein encoding gene (CPLX3). A total of 350 unrelated individuals of Armenian nationality (175 SCZ patients and the same number of age-, sex-matched healthy controls) were genotyped for the selected polymorphism using polymerase chain reaction with sequence-specific primers. Results and main findings: According to the results obtained, the frequency and carriage of the CPLX3 rs3743487*T allele did not differ in SCZ patients as compared to controls. Conclusions: We concluded that the CPLX3 rs3743487*T minor allele is not associated with SCZ in Armenian population. Brief summary: This study suggested no association of the CPLX3 rs3743487 polymorphism with schizophrenia, however, to clarify the role of the CPLX3 gene in SCZ further studies with much coverage of the gene and involvement of different methods are required.

Authors: Atshemyan Sofi, Zakharyan Roksana, Arakelyan Arsen

Date Published: 30th Dec 2015

Publication Type: Journal

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