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Boulenouar H, Benhatchi H, Guermoudi F, Oumiloud AH, Rahoui A. An actualized screening of schizophrenia-associated genes. EGYPTIAN JOURNAL OF MEDICAL HUMAN GENETICS 2022. [DOI: 10.1186/s43042-022-00269-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Schizophrenia is a psychotic disorder that impacts around 0.5% to 1.2% of the world's population. It has been well established that heredity plays an essential role in the causation of schizophrenia, with genetic heritability of up to 80%. A several new schizophrenia susceptibility genes were identified at the start of the twenty-first century. The aim of this systematic review will be to explore the association between single nucleotide polymorphisms (SNPs) and schizophrenia risk in people all over the world.
Methods
This systematic review collected available data on genetic variants associated with schizophrenia in worldwide populations. A PubMed and Science Direct search was investigated to identify all studies published until December 2020 on genetic susceptibility to schizophrenia in various populations, excluding family studies, transversal studies, cohort studies, experimental studies, and descriptive studies; those that demonstrate an association between repeat polymorphism (CNV, VNTR, etc.). All researches on genetic predispositions of schizophrenia and accepting the predetermined inclusion criteria were included in this systematic review.
Findings
Thirty-six studies focused on the schizophrenia-associated genes were retained in which a total of 44 polymorphisms among 26 susceptibility genes to schizophrenia have been associated in the world populations.
Conclusion
Despite the few number of studies published about genetic of schizophrenia, some genetic variations have been consistently correlated to schizophrenia, particularly in China, as this analysis shows. Further data, especially from genome-wide association studies, might contribute in the development of a reference for schizophrenia genetic susceptibility markers.
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Bernstein HG, Keilhoff G, Laube G, Dobrowolny H, Steiner J. Polyamines and polyamine-metabolizing enzymes in schizophrenia: Current knowledge and concepts of therapy. World J Psychiatry 2021; 11:1177-1190. [PMID: 35070769 PMCID: PMC8717027 DOI: 10.5498/wjp.v11.i12.1177] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Revised: 04/30/2021] [Accepted: 11/25/2021] [Indexed: 02/06/2023] Open
Abstract
Polyamines play preeminent roles in a variety of cellular functions in the central nervous system and other organs. A large body of evidence suggests that the polyamine pathway is prominently involved in the etiology and pathology of schizophrenia. Alterations in the expression and activity of polyamine metabolizing enzymes, as well as changes in the levels of the individual polyamines, their precursors and derivatives, have been measured in schizophrenia and animal models of the disease. Additionally, neuroleptic treatment has been shown to influence polyamine concentrations in brain and blood of individuals with schizophrenia. Thus, the polyamine system may appear to be a promising target for neuropharmacological treatment of schizophrenia. However, for a number of practical reasons there is currently only limited hope for a polyamine-based schizophrenia therapy.
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Affiliation(s)
- Hans-Gert Bernstein
- Department of Psychiatry, University of Magdeburg, Magdeburg D-39116, Saxony-Anhalt, Germany
| | - Gerburg Keilhoff
- Institute of Biochemistry and Cell Biology, University of Magdeburg, Magdeburg D-39116, Saxony-Anhalt, Germany
| | - Gregor Laube
- Department of Anatomy, Charite, Berlin D-10117, Germany
| | - Henrik Dobrowolny
- Department of Psychiatry, University of Magdeburg, Magdeburg D-39116, Saxony-Anhalt, Germany
| | - Johann Steiner
- Department of Psychiatry, University of Magdeburg, Magdeburg D-39116, Saxony-Anhalt, Germany
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Aishwarya S, Gunasekaran K, Margret AA. Computational gene expression profiling in the exploration of biomarkers, non-coding functional RNAs and drug perturbagens for COVID-19. J Biomol Struct Dyn 2020; 40:3681-3696. [PMID: 33228475 PMCID: PMC7754930 DOI: 10.1080/07391102.2020.1850360] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
The coronavirus disease, caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is a global health crisis that is being endured with an increased alarm of transmission each day. Though the pandemic has activated innumerable research attention to decipher an antidote, fundamental understanding of the molecular mechanisms is necessary to halt the disease progression. The study focused on comparison of the COVID-19 infected lung tissue gene expression datasets -GSE155241 and GSE150316 with the GEO2R-limma package. The significant up- and downregulated genes were annotated. Further evaluation of the enriched pathways, transcription factors, kinases, noncoding RNAs and drug perturbations revealed the significant molecular mechanisms of the host response. The results revealed a surge in mitochondrial respiration, cytokines, neurodegenerative mechanisms and deprived oxygen, iron, copper, and glucose transport. Hijack of ubiquitination by SARS-CoV-2, hox gene differentiation, histone modification, and miRNA biogenesis were the notable molecular mechanisms inferred. Long non-coding RNAs such as C058791.1, TTTY15 and TPTEP1 were predicted to be efficient in regulating the disease mechanisms. Drugs-F-1566-0341, Digoxin, Proscillaridin and Linifanib that reverse the gene expression signatures were predicted from drug perturbations analysis. The binding efficiency and interaction of proscillaridin and digoxin as obtained from the molecular docking studies confirmed their therapeutic potential. Two overlapping upregulated genes MDH1, SGCE and one downregulated gene PFKFB3 were appraised as potential biomarkers candidates. The upregulation of PGM5, ISLR and ANK2 as measured from their expressions in normal lungs affirmed their possible prognostic biomarker competence. The study explored significant insights for better diagnosis, and therapeutic options for COVID-19. Communicated by Ramaswamy H. Sarma
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Affiliation(s)
- S Aishwarya
- Department of Bioinformatics, Stella Maris College, Chennai, Tamil Nadu, India.,Centre of Advanced Study in Crystallography and Biophysics, University of Madras, Chennai, Tamil Nadu, India
| | - K Gunasekaran
- Centre of Advanced Study in Crystallography and Biophysics, University of Madras, Chennai, Tamil Nadu, India
| | - A Anita Margret
- Department of Biotechnology, Bishop Heber College, Tiruchirappalli, Tamil Nadu, India
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Lack of association of SNPs from the FADS1-FADS2 gene cluster with major depression or suicidal behavior. Psychiatr Genet 2016; 26:81-6. [PMID: 26513616 DOI: 10.1097/ypg.0000000000000111] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
Fatty acid desaturase genes (FADS1-FADS2) encode desaturases participating in the biosynthesis of long-chain polyunsaturated fatty acids. As long-chain polyunsaturated fatty acids are implicated in major depressive disorder (MDD) and suicide risk, and as both are partly heritable, we studied the association of FADS1-FADS2 polymorphisms with MDD (635 cases, 480 controls) and suicide attempt status (291 attempters, 344 MDD nonattempters). Eighteen FADS-related single-nucleotide polymorphisms were genotyped from Caucasians enrolled in Madrid (n=791) or New York City (n=324) and entered as predictors into logistic regression analyses with diagnostic group or suicide attempt history as outcomes and location and sex as covariates. No associations were observed between any single-nucleotide polymorphisms and diagnosis or attempt status. As statistical power was adequate, we conclude that FADS1-FADS2 genetic variants may not be a common determinant of MDD.
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Coker-Gürkan A, Arisan S, Arisan ED, Unsal NP. Lack of evidence for the association of ornithine decarboxylase (+316 G>A), spermidine/spermine acetyl transferase (-1415 T>C) gene polymorphisms with calcium oxalate stone disease. Biomed Rep 2013; 2:69-74. [PMID: 24649071 DOI: 10.3892/br.2013.184] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2013] [Accepted: 09/20/2013] [Indexed: 12/19/2022] Open
Abstract
Urolithiasis is a complex and multifactorial disorder characterized by the presence of stones in the urinary tract. Urea cycle is an important process involved in disease progression. L-ornithine is a key amino acid in the urea cycle and is converted to putrescine by ornithine decarboxylase (ODC). Putrescine, spermidine and spermine are natural polyamines that are catabolized by a specific enzyme, spermidine/spermine acetyltransferase (SSAT). The single-nucleotide polymorphisms (SNPs) in the intron region of ODC (+316 G>A) and promoter region of SSAT (-1415 T>C) genes have been found to be associated with the polyamines expression levels. The aim of this study was to examine whether the ODC (+316 G>A) intron 1 region gene polymorphism and SAT-1 promoter region (-1415 T>C) gene polymorphisms are potential genetic markers for susceptibility to urolithiasis. A control group of 104 healthy subjects and a group of 65 patients with recurrent idiopathic calcium oxalate stone disease were enrolled into this study. Polymerase chain reaction (PCR)-based restriction analysis was performed for the ODC intron 1 (+316 G>A) region and SAT-1 (-1415 T>C) promoter gene polymorphisms by PstI and MspI restriction enzyme digestion, respectively. The genotype distribution of polymorphisms studied in the ODC intron 1 region (+316 G>A) and SAT-1 -1415 T>C promoter region did not reveal a significant difference between urolithiasis and the control groups (P=0.713 and 0.853), respectively. Furthermore, no significant difference was observed between the control and patient groups for ODC +316 G>A and SAT-1 -1415 T>C allele frequencies (P=0.877 and 0.644), respectively. In conclusion, results of the present study suggest that ODC + 316 G>A and SAT-1 -1415 T>C gene polymorphisms might not be a risk factor for urolithiasis.
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Affiliation(s)
- Ajda Coker-Gürkan
- Department of Molecular Biology and Genetics, Science and Letter Faculty, Istanbul Kultur University, Atakoy Campus, 34156 Istanbul, Turkey
| | - Serdar Arisan
- 1st Urology Clinics, Şişli Etfal Research and Training Hospital, Sisli, 34377 Istanbul, Turkey
| | - Elif Damla Arisan
- Department of Molecular Biology and Genetics, Science and Letter Faculty, Istanbul Kultur University, Atakoy Campus, 34156 Istanbul, Turkey
| | - Narçin Palavan Unsal
- Department of Molecular Biology and Genetics, Science and Letter Faculty, Istanbul Kultur University, Atakoy Campus, 34156 Istanbul, Turkey
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Cacabelos R, Cacabelos P, Aliev G. Genomics of schizophrenia and pharmacogenomics of antipsychotic drugs. ACTA ACUST UNITED AC 2013. [DOI: 10.4236/ojpsych.2013.31008] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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Riaza Bermudo-Soriano C, Perez-Rodriguez MM, Vaquero-Lorenzo C, Baca-Garcia E. New perspectives in glutamate and anxiety. Pharmacol Biochem Behav 2011; 100:752-74. [PMID: 21569789 DOI: 10.1016/j.pbb.2011.04.010] [Citation(s) in RCA: 147] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2010] [Revised: 04/05/2011] [Accepted: 04/15/2011] [Indexed: 02/07/2023]
Abstract
Anxiety and stress-related disorders, namely posttraumatic stress disorder (PTSD), generalized anxiety disorder (GAD), obsessive-compulsive disorder (ODC), social and specific phobias, and panic disorder, are a major public health issue. A growing body of evidence suggests that glutamatergic neurotransmission may be involved in the biological mechanisms underlying stress response and anxiety-related disorders. The glutamatergic system mediates the acquisition and extinction of fear-conditioning. Thus, new drugs targeting glutamatergic neurotransmission may be promising candidates for new pharmacological treatments. In particular, N-methyl-d-aspartate receptors (NMDAR) antagonists (AP5, AP7, CGP37849, CGP39551, LY235959, NPC17742, and MK-801), NMDAR partial agonists (DCS, ACPC), α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptors (AMPARs) antagonists (topiramate), and several allosteric modulators targeting metabotropic glutamate receptors (mGluRs) mGluR1, mGluR2/3, and mGluR5, have shown anxiolytic-like effects in several animal and human studies. Several studies have suggested that polyamines (agmatine, putrescine, spermidine, and spermine) may be involved in the neurobiological mechanisms underlying stress-response and anxiety-related disorders. This could mainly be attributed to their ability to modulate ionotropic glutamate receptors, especially NR2B subunits. The aim of this review is to establish that glutamate neurotransmission and polyaminergic system play a fundamental role in the onset of anxiety-related disorders. This may open the way for new drugs that may help to treat these conditions.
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Fiori LM, Wanner B, Jomphe V, Croteau J, Vitaro F, Tremblay RE, Bureau A, Turecki G. Association of polyaminergic loci with anxiety, mood disorders, and attempted suicide. PLoS One 2010; 5:e15146. [PMID: 21152090 PMCID: PMC2994870 DOI: 10.1371/journal.pone.0015146] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2010] [Accepted: 10/26/2010] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND The polyamine system has been implicated in a number of psychiatric conditions, which display both alterations in polyamine levels and altered expression of genes related to polyamine metabolism. Studies have identified associations between genetic variants in spermidine/spermine N1-acetyltransferase (SAT1) and both anxiety and suicide, and several polymorphisms appear to play important roles in determining gene expression. METHODOLOGY/PRINCIPAL FINDINGS We genotyped 63 polymorphisms, spread across four polyaminergic genes (SAT1, spermine synthase (SMS), spermine oxidase (SMOX), and ornithine aminotransferase like-1 (OATL1)), in 1255 French-Canadian individuals who have been followed longitudinally for 22 years. We assessed univariate associations with anxiety, mood disorders, and attempted suicide, as assessed during early adulthood. We also investigated the involvement of gene-environment interactions in terms of childhood abuse, and assessed internalizing and externalizing symptoms as endophenotypes mediating these interactions. Overall, each gene was associated with at least one main outcome: anxiety (SAT1, SMS), mood disorders (SAT1, SMOX), and suicide attempts (SAT1, OATL1). Several SAT1 polymorphisms displayed disease-specific risk alleles, and polymorphisms in this gene were involved in gene-gene interactions with SMS to confer risk for anxiety disorders, as well as gene-environment interactions between childhood physical abuse and mood disorders. Externalizing behaviors demonstrated significant mediation with regards to the association between OATL1 and attempted suicide, however there was no evidence that externalizing or internalizing behaviors were appropriate endophenotypes to explain the associations with mood or anxiety disorders. Finally, childhood sexual abuse did not demonstrate mediating influences on any of our outcomes. CONCLUSIONS/SIGNIFICANCE These results demonstrate that genetic variants in polyaminergic genes are associated with psychiatric conditions, each of which involves a set of separate and distinct risk alleles. As several of these polymorphisms are associated with gene expression, these findings may provide mechanisms to explain the alterations in polyamine metabolism which have been observed in psychiatric disorders.
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Affiliation(s)
- Laura M. Fiori
- McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada
| | - Brigitte Wanner
- Research Unit on Children's Psychosocial Maladjustment, Université de Montréal, Montreal, Quebec, Canada
| | - Valérie Jomphe
- Centre de recherche Université Laval Robert-Giffard, Université Laval, Quebec City, Quebec, Canada
| | - Jordie Croteau
- Centre de recherche Université Laval Robert-Giffard, Université Laval, Quebec City, Quebec, Canada
| | - Frank Vitaro
- Research Unit on Children's Psychosocial Maladjustment, Université de Montréal, Montreal, Quebec, Canada
| | - Richard E. Tremblay
- Research Unit on Children's Psychosocial Maladjustment, Université de Montréal, Montreal, Quebec, Canada
- School of Public Health and Population Sciences, University College Dublin, Dublin, Ireland
| | - Alexandre Bureau
- Centre de recherche Université Laval Robert-Giffard, Université Laval, Quebec City, Quebec, Canada
| | - Gustavo Turecki
- McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada
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Fiori LM, Turecki G. Association of the SAT1 in/del polymorphism with suicide completion. Am J Med Genet B Neuropsychiatr Genet 2010; 153B:825-9. [PMID: 19851986 DOI: 10.1002/ajmg.b.31040] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Several studies have observed decreased expression of spermidine/spermine N1-acetyltransferase (SAT1) in the brains of suicide completers, and we previously identified a single-nucleotide polymorphism in the promoter region of SAT1 which was associated with suicide completion and SAT1 expression in the brain. We recently characterized the haplotype structure of the SAT1 promoter region and identified an insertion/deletion (in/del) of 15 adenine residues. This variant appears to be a predictor of SAT1 expression, and we were thus interested in determining if the lower expressing deletion allele was found more frequently among suicide completers. To this end, we genotyped the in/del in a sample of 771 French-Canadian males, comprising 326 suicide completers and 445 non-suicide controls. We found no significant difference in the frequencies of the two alleles between suicide completers and controls in the entire sample. However, we observed a significantly higher frequency of the deletion in the depressed suicide completers compared to the depressed non-suicides. These results add support for a role of SAT1 in conferring a risk for suicide completion, in particular in the context of depressive disorders.
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Affiliation(s)
- Laura M Fiori
- McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada
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