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Genetic Variations Associated with Brain Disorders: Focus on Synaptic Plasticity and Apoptosis Regulatory Genes in Schizophrenia, Posttraumatic Stress Disorder and Ischemic Stroke
International Journal of Genetics and Genomics
Volume 2, Issue 2, April 2014, Pages: 19-29
Received: Apr. 20, 2014; Accepted: May 20, 2014; Published: May 30, 2014
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Anna Boyajyan, Laboratory of Human Genomics and Immunomics, Department of Applied Molecular Biology, Institute of Molecular Biology NAS RA, Yerevan, Armenia
Ani Stepanyan, Laboratory of Human Genomics and Immunomics, Department of Applied Molecular Biology, Institute of Molecular Biology NAS RA, Yerevan, Armenia
Diana Avetyan, Laboratory of Human Genomics and Immunomics, Department of Applied Molecular Biology, Institute of Molecular Biology NAS RA, Yerevan, Armenia
Hovsep Ghazaryan, Laboratory of Human Genomics and Immunomics, Department of Applied Molecular Biology, Institute of Molecular Biology NAS RA, Yerevan, Armenia
Sofi Atshemyan, Laboratory of Human Genomics and Immunomics, Department of Applied Molecular Biology, Institute of Molecular Biology NAS RA, Yerevan, Armenia
Roksana Zakharyan, Laboratory of Human Genomics and Immunomics, Department of Applied Molecular Biology, Institute of Molecular Biology NAS RA, Yerevan, Armenia
Kristina Pirumyan, Laboratory of Human Genomics and Immunomics, Department of Applied Molecular Biology, Institute of Molecular Biology NAS RA, Yerevan, Armenia
Gohar Tsakanova, Laboratory of Human Genomics and Immunomics, Department of Applied Molecular Biology, Institute of Molecular Biology NAS RA, Yerevan, Armenia
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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.
Schizophrenia, Posttraumatic Stress Disorder, Ischemic Stroke, Synaptic Plasticity, Apoptosis, Regulatory Genes, Single Nucleotide Polymorphisms, Genotyping, Association
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Anna Boyajyan, Ani Stepanyan, Diana Avetyan, Hovsep Ghazaryan, Sofi Atshemyan, Roksana Zakharyan, Kristina Pirumyan, Gohar Tsakanova, Genetic Variations Associated with Brain Disorders: Focus on Synaptic Plasticity and Apoptosis Regulatory Genes in Schizophrenia, Posttraumatic Stress Disorder and Ischemic Stroke, International Journal of Genetics and Genomics. Vol. 2, No. 2, 2014, pp. 19-29. doi: 10.11648/j.ijgg.20140202.12
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