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Ryszard Wiaderkiewicz - One of the best experts on this subject based on the ideXlab platform.
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selected single nucleotide variants in grin1 grin2a and GRIN2B encoding subunits of the nmda receptor are not biomarkers of schizophrenia resistant to clozapine exploratory study
Pharmacological Reports, 2021Co-Authors: Marek Krzystanek, Marek Asman, Joanna Witecka, Artur Palasz, Ryszard WiaderkiewiczAbstract:Schizophrenia is a common mental illness whose pathogenesis is still unknown. The vulnerability and stress model in schizophrenia assume that susceptibility to the disease is mainly associated with genes. Of the five symptomatic dimensions of schizophrenia, cognitive impairment appears to be most associated with the pathogenesis of schizophrenia. The aim of the study was to explore whether selected nucleotide variants in GRIN1, GRIN2A, and GRIN2B encoding subunits of the N-methyl-d-aspartate receptor (NMDA-R) receptor occur in a selected group of patients with treatment resistant schizophrenia with cognitive impairment. The study included 45 patients diagnosed with super refractory schizophrenia, all with cognitive deficits and chronically psychotic. DNA fragments including the studied polymorphisms of the NMDA receptors subunit genes were amplified by polymerase chain reaction and subjected to sequencing. The study did not confirm the presence of any of the four selected single-nucleotide variants in GRIN1, GRIN2A, and GRIN2B subunits of NMDA-R in the study group. Results of the study indicated that the selected single-nucleotide variants are not associated both with resistance to clozapine and the presence of cognitive deficits in schizophrenia. It is possible, however, that a more extensive sequencing along with analyzing the expression of these genes may reveal different single-nucleotide variants than those assumed in the study.
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Exploratory study of selected nucleotide variants in GRIN1, GRIN2A and GRIN2B encoding subunits of the NMDA receptor in a targeted group of schizophrenia patients with chronic cognitive impairment.
Pharmacological reports : PR, 2020Co-Authors: Marek Krzystanek, Marek Asman, Joanna Witecka, Artur Pałasz, Ryszard WiaderkiewiczAbstract:Schizophrenia is a mental disease that affects approximately 1% of the population. Despite over 100 years of research, its pathomechanism has still not been clarified. Cognitive deficits, which are one of the symptomatic dimensions of schizophrenia, usually appear a few years before the first psychotic episode. Therefore, this is why they are probably the clinical manifestation of the primary pathomechanism of schizophrenia. It is also supposed that N-methyl-D-aspartate receptor (NMDA-R) insufficiency in the prefrontal cortex is responsible for cognitive deficits in schizophrenia. The study aimed to examine whether four selected single nucleotide variants in GRIN1, GRIN2A and GRIN2B encoding NMDA-R subunits, of which two have not been tested before, are linked with the selected clinical phenotype of cognitive dysfunction in schizophrenia. The study included the targeted group of 117 patients diagnosed with schizophrenia, all with cognitive deficits and in symptomatic remission. DNA fragments including the studied polymorphisms of the NMDA receptors subunit genes were amplified by polymerase chain reaction and subjected to sequencing. The study did not confirm the presence of any of the four selected single nucleotide variants in GRIN1, GRIN2A and GRIN2B subunits of NMDA-R. The finding indicates that selected single nucleotide variants in GRIN2A and GRIN2B encoding subunits of the NMDA receptor are not associated with the presence of cognitive deficits in schizophrenia.
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Exploratory study of selected nucleotide variants in GRIN1, GRIN2A and GRIN2B encoding subunits of the NMDA receptor in a targeted group of schizophrenia patients with chronic cognitive impairment
Pharmacological Reports, 2020Co-Authors: Marek Krzystanek, Marek Asman, Joanna Witecka, Artur Pałasz, Ryszard WiaderkiewiczAbstract:Background Schizophrenia is a mental disease that affects approximately 1% of the population. Despite over 100 years of research, its pathomechanism has still not been clarified. Cognitive deficits, which are one of the symptomatic dimensions of schizophrenia, usually appear a few years before the first psychotic episode. Therefore, this is why they are probably the clinical manifestation of the primary pathomechanism of schizophrenia. It is also supposed that N -methyl- d -aspartate receptor (NMDA-R) insufficiency in the prefrontal cortex is responsible for cognitive deficits in schizophrenia. The study aimed to examine whether four selected single nucleotide variants in GRIN1 , GRIN2A and GRIN2B encoding NMDA-R subunits, of which two have not been tested before, are linked with the selected clinical phenotype of cognitive dysfunction in schizophrenia. Methods The study included the targeted group of 117 patients diagnosed with schizophrenia, all with cognitive deficits and in symptomatic remission. DNA fragments including the studied polymorphisms of the NMDA receptors subunit genes were amplified by polymerase chain reaction and subjected to sequencing. Results The study did not confirm the presence of any of the four selected single nucleotide variants in GRIN1 , GRIN2A and GRIN2B subunits of NMDA-R. Conclusions The finding indicates that selected single nucleotide variants in GRIN2A and GRIN2B encoding subunits of the NMDA receptor are not associated with the presence of cognitive deficits in schizophrenia.
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Selected single-nucleotide variants in GRIN1, GRIN2A, and GRIN2B encoding subunits of the NMDA receptor are not biomarkers of schizophrenia resistant to clozapine: exploratory study
Pharmacological Reports, 2020Co-Authors: Marek Krzystanek, Marek Asman, Joanna Witecka, Artur Pałasz, Ryszard WiaderkiewiczAbstract:Background Schizophrenia is a common mental illness whose pathogenesis is still unknown. The vulnerability and stress model in schizophrenia assume that susceptibility to the disease is mainly associated with genes. Of the five symptomatic dimensions of schizophrenia, cognitive impairment appears to be most associated with the pathogenesis of schizophrenia. The aim of the study was to explore whether selected nucleotide variants in GRIN1 , GRIN2A , and GRIN2B encoding subunits of the N -methyl- d -aspartate receptor (NMDA-R) receptor occur in a selected group of patients with treatment resistant schizophrenia with cognitive impairment. Methods The study included 45 patients diagnosed with super refractory schizophrenia, all with cognitive deficits and chronically psychotic. DNA fragments including the studied polymorphisms of the NMDA receptors subunit genes were amplified by polymerase chain reaction and subjected to sequencing. Results The study did not confirm the presence of any of the four selected single-nucleotide variants in GRIN1 , GRIN2A , and GRIN2B subunits of NMDA-R in the study group. Conclusion Results of the study indicated that the selected single-nucleotide variants are not associated both with resistance to clozapine and the presence of cognitive deficits in schizophrenia. It is possible, however, that a more extensive sequencing along with analyzing the expression of these genes may reveal different single-nucleotide variants than those assumed in the study.
Christian Beste - One of the best experts on this subject based on the ideXlab platform.
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n methyl d aspartate receptor 2b subunit GRIN2B gene variation is associated with alerting but not with orienting and conflicting in the attention network test
Neuropharmacology, 2012Co-Authors: Stefanie Schulz, Larissa Arning, Marlies Pinnow, Jorg T Epplen, Christian BesteAbstract:Appropriate attention levels are pivotal for cognitive processes, and individual differences in attentional functioning are related to variations in the interplay of neurotransmitters. The attention network theory reflects attention as a non-homogenous set of separate neural networks: alerting, orienting and conflicting. In the present study, the role of variations in GRIN2B, which encodes the NR2B subunit of Nmethyl-D-aspartate (NMDA) receptors, was explored with regard to the regulation of arousal and attention by comparing the efficiency of the three attentional networks as measured with the Attention Network Test (ANT). Two synonymous SNPs in GRIN2B, rs1806201 (T888T) and rs1806191 (H1178H) were genotyped in 324 young Caucasian adults. Results revealed a highly specific modulatory influence of SNP rs1806201 on alerting processes with subjects homozygous for the frequent C allele displaying higher alerting network scores as compared to the other two genotype groups (CT and TT). This effect is due to the fact that in the no cue condition faster reaction times were evident in participants carrying at least one of the rare T alleles, possibly as a result of more effective glutamatergic neurotransmission. The results might be further explained by a dissociation between tonic and phasic alertness modulated by the GRIN2B genotype and by a ceiling effect, meaning that subjects cannot be phasicly alert in excess to a certain level. Altogether, the results show that variations in GRIN2B have to be taken into consideration when examining attentional processes.
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variation in the nmda receptor 2b subunit gene GRIN2B is associated with differential language lateralization
Behavioural Brain Research, 2011Co-Authors: Sebastian Ocklenburg, Larissa Arning, Jorg T Epplen, Constanze Hahn, Wanda M Gerding, Onur Gunturkun, Christian BesteAbstract:Variations in the N-methyl-d-aspartate receptor 2B subunit gene (GRIN2B) have been associated with schizophrenia, a psychiatric disorder associated with reduced left-hemispheric language dominance. Here, we investigated, whether different polymorphisms in GRIN2B influence language lateralization and handedness in healthy individuals. In a cohort of 424 genetically unrelated participants we found significant association between the synonymous GRIN2B variation rs1806201 and language lateralization assessed using the dichotic listening task. Individuals carrying the heterozygous CT genotype exhibited more pronounced left-hemispheric language dominance as compared to both homozygous CC and TT individuals. Such an association was not identified for handedness. These findings suggest that variation in NMDA-receptors contributes to the interindividual variability of language lateralization.
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variations in the GRIN2B gene are associated with risky decision making
Neuropharmacology, 2011Co-Authors: Vanessa Ness, Larissa Arning, Jorg T Epplen, Hanna E Niesert, Maik C Stuttgen, Christian BesteAbstract:The dopaminergic system is known to modulate decision-making. As N-methyl-D-aspartate (NMDA) receptors strongly influence dopaminergic function, it is conceivable that the glutamatergic system is also involved in decision-making. We examined whether polymorphisms in the N-methyl-d-aspartate receptor 2B subunit gene (GRIN2B) influence decision-making using the Iowa Gambling Task (IGT). In total, 245 (n = 245, 127 female) healthy German students were included in the analysis. Two synonymous SNPs in exon 13, rs1806191 (H1178H) and rs1806201 (T888T) showed the strongest association with aspects of IGT performance. Females with a CC allele in rs1806201 made less use both of a win-stay strategy and demonstrated more exploratory behaviour during task execution. For rs1806191, we found a strong additive effect in usage of a win-stay strategy. This, partly sex-dependent, correlation of the win-stay/lose-shift behaviour with GRIN2B genotypes suggests that healthy individuals with certain GRIN2B variations respond differently to ambiguous conditions, possibly by altered perception of wins and losses. These findings underline the necessity to integrate the glutamatergic system when examining decision-making processes.
Jianping Jia - One of the best experts on this subject based on the ideXlab platform.
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association between nr2b subunit gene GRIN2B promoter polymorphisms and sporadic alzheimer s disease in the north chinese population
Neuroscience Letters, 2009Co-Authors: Hanqiu Jiang, Jianping JiaAbstract:N-methyl-d-aspartate (NMDA) receptor plays a crucial role in learning, memory and information processing of human brain. Its dysfunction is related to the pathogenesis of Alzheimer's disease (AD). We detected four polymorphisms of the promoter regions of the human NMDA receptor 2B (NR2B) subunit gene (GRIN2B) in 362 AD patients and 334 healthy in North Han Chinese populations, these were -200T/G (rs1019385), -421C/A (rs3764028), -1447T/C (ENS10557853), and -1497G/A (rs12368476). Genetic analysis confirmed that there were significant differences in genotype (P=0.029) and allele (P=0.010) frequencies for -421C/A between SAD and control. In the subjects without APOE varepsilon4 allele, these difference remained significant (genotype P=0.012, allele P=0.004). The -421CC genotype was about 1.5 fold increasing risk compared with CA+AA genotypes (OR=1.517, 95% CI 1.077-2.137, P=0.017). Luciferase reporter assay showed a 34.69-39.79% decrease in transcriptional activity for -421C allele of GRIN2B promoter compared with -421A in SH-SY5Y and HeLa cell lines. Our study suggests that the -421C allele may induce lower GRIN2B transcriptional activity and NR2B protein expression, thus it is associated with AD.
Marek Krzystanek - One of the best experts on this subject based on the ideXlab platform.
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selected single nucleotide variants in grin1 grin2a and GRIN2B encoding subunits of the nmda receptor are not biomarkers of schizophrenia resistant to clozapine exploratory study
Pharmacological Reports, 2021Co-Authors: Marek Krzystanek, Marek Asman, Joanna Witecka, Artur Palasz, Ryszard WiaderkiewiczAbstract:Schizophrenia is a common mental illness whose pathogenesis is still unknown. The vulnerability and stress model in schizophrenia assume that susceptibility to the disease is mainly associated with genes. Of the five symptomatic dimensions of schizophrenia, cognitive impairment appears to be most associated with the pathogenesis of schizophrenia. The aim of the study was to explore whether selected nucleotide variants in GRIN1, GRIN2A, and GRIN2B encoding subunits of the N-methyl-d-aspartate receptor (NMDA-R) receptor occur in a selected group of patients with treatment resistant schizophrenia with cognitive impairment. The study included 45 patients diagnosed with super refractory schizophrenia, all with cognitive deficits and chronically psychotic. DNA fragments including the studied polymorphisms of the NMDA receptors subunit genes were amplified by polymerase chain reaction and subjected to sequencing. The study did not confirm the presence of any of the four selected single-nucleotide variants in GRIN1, GRIN2A, and GRIN2B subunits of NMDA-R in the study group. Results of the study indicated that the selected single-nucleotide variants are not associated both with resistance to clozapine and the presence of cognitive deficits in schizophrenia. It is possible, however, that a more extensive sequencing along with analyzing the expression of these genes may reveal different single-nucleotide variants than those assumed in the study.
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Exploratory study of selected nucleotide variants in GRIN1, GRIN2A and GRIN2B encoding subunits of the NMDA receptor in a targeted group of schizophrenia patients with chronic cognitive impairment.
Pharmacological reports : PR, 2020Co-Authors: Marek Krzystanek, Marek Asman, Joanna Witecka, Artur Pałasz, Ryszard WiaderkiewiczAbstract:Schizophrenia is a mental disease that affects approximately 1% of the population. Despite over 100 years of research, its pathomechanism has still not been clarified. Cognitive deficits, which are one of the symptomatic dimensions of schizophrenia, usually appear a few years before the first psychotic episode. Therefore, this is why they are probably the clinical manifestation of the primary pathomechanism of schizophrenia. It is also supposed that N-methyl-D-aspartate receptor (NMDA-R) insufficiency in the prefrontal cortex is responsible for cognitive deficits in schizophrenia. The study aimed to examine whether four selected single nucleotide variants in GRIN1, GRIN2A and GRIN2B encoding NMDA-R subunits, of which two have not been tested before, are linked with the selected clinical phenotype of cognitive dysfunction in schizophrenia. The study included the targeted group of 117 patients diagnosed with schizophrenia, all with cognitive deficits and in symptomatic remission. DNA fragments including the studied polymorphisms of the NMDA receptors subunit genes were amplified by polymerase chain reaction and subjected to sequencing. The study did not confirm the presence of any of the four selected single nucleotide variants in GRIN1, GRIN2A and GRIN2B subunits of NMDA-R. The finding indicates that selected single nucleotide variants in GRIN2A and GRIN2B encoding subunits of the NMDA receptor are not associated with the presence of cognitive deficits in schizophrenia.
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Exploratory study of selected nucleotide variants in GRIN1, GRIN2A and GRIN2B encoding subunits of the NMDA receptor in a targeted group of schizophrenia patients with chronic cognitive impairment
Pharmacological Reports, 2020Co-Authors: Marek Krzystanek, Marek Asman, Joanna Witecka, Artur Pałasz, Ryszard WiaderkiewiczAbstract:Background Schizophrenia is a mental disease that affects approximately 1% of the population. Despite over 100 years of research, its pathomechanism has still not been clarified. Cognitive deficits, which are one of the symptomatic dimensions of schizophrenia, usually appear a few years before the first psychotic episode. Therefore, this is why they are probably the clinical manifestation of the primary pathomechanism of schizophrenia. It is also supposed that N -methyl- d -aspartate receptor (NMDA-R) insufficiency in the prefrontal cortex is responsible for cognitive deficits in schizophrenia. The study aimed to examine whether four selected single nucleotide variants in GRIN1 , GRIN2A and GRIN2B encoding NMDA-R subunits, of which two have not been tested before, are linked with the selected clinical phenotype of cognitive dysfunction in schizophrenia. Methods The study included the targeted group of 117 patients diagnosed with schizophrenia, all with cognitive deficits and in symptomatic remission. DNA fragments including the studied polymorphisms of the NMDA receptors subunit genes were amplified by polymerase chain reaction and subjected to sequencing. Results The study did not confirm the presence of any of the four selected single nucleotide variants in GRIN1 , GRIN2A and GRIN2B subunits of NMDA-R. Conclusions The finding indicates that selected single nucleotide variants in GRIN2A and GRIN2B encoding subunits of the NMDA receptor are not associated with the presence of cognitive deficits in schizophrenia.
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Selected single-nucleotide variants in GRIN1, GRIN2A, and GRIN2B encoding subunits of the NMDA receptor are not biomarkers of schizophrenia resistant to clozapine: exploratory study
Pharmacological Reports, 2020Co-Authors: Marek Krzystanek, Marek Asman, Joanna Witecka, Artur Pałasz, Ryszard WiaderkiewiczAbstract:Background Schizophrenia is a common mental illness whose pathogenesis is still unknown. The vulnerability and stress model in schizophrenia assume that susceptibility to the disease is mainly associated with genes. Of the five symptomatic dimensions of schizophrenia, cognitive impairment appears to be most associated with the pathogenesis of schizophrenia. The aim of the study was to explore whether selected nucleotide variants in GRIN1 , GRIN2A , and GRIN2B encoding subunits of the N -methyl- d -aspartate receptor (NMDA-R) receptor occur in a selected group of patients with treatment resistant schizophrenia with cognitive impairment. Methods The study included 45 patients diagnosed with super refractory schizophrenia, all with cognitive deficits and chronically psychotic. DNA fragments including the studied polymorphisms of the NMDA receptors subunit genes were amplified by polymerase chain reaction and subjected to sequencing. Results The study did not confirm the presence of any of the four selected single-nucleotide variants in GRIN1 , GRIN2A , and GRIN2B subunits of NMDA-R in the study group. Conclusion Results of the study indicated that the selected single-nucleotide variants are not associated both with resistance to clozapine and the presence of cognitive deficits in schizophrenia. It is possible, however, that a more extensive sequencing along with analyzing the expression of these genes may reveal different single-nucleotide variants than those assumed in the study.
Soon Ae Kim - One of the best experts on this subject based on the ideXlab platform.
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Family based association of GRIN2A and GRIN2B with Korean autism spectrum disorders.
Neuroscience letters, 2012Co-Authors: Hee Jeong Yoo, In Hee Cho, Mira Park, So Young Yang, Soon Ae KimAbstract:Abstract N -Methyl- d -aspartate (NMDA) receptor, one of the glutamate receptors, has a role in the regulation of synaptic activity. It functions as an ion channel in the central nervous system and its inappropriate activation has been implicated in several neurological conditions. To test the association between candidate genes related with NMDA receptors and autism spectrum disorders (ASDs), we examined single nucleotide polymorphisms (SNPs) for GRIN2A and GRIN2B by using the family-based association test (FBAT) in 151 Korean trios. There was a statistically significant associations between ASDs and haplotypes in GRIN2B (bi-allelic mode additive model P -value = 0.003; FDR P -value = 0.012). This study supports a possible role of GRIN2B as a candidate gene for the etiology of ASDs.
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association study of polymorphisms in n methyl d aspartate receptor 2b subunits GRIN2B gene with korean alcoholism
Neuroscience Research, 2006Co-Authors: Jin Hee Kim, Jooho Chung, Hee Jeong Yoo, Mira Park, So Young Yang, Bumseok Jeong, Jong Woo Kim, Soon Ae KimAbstract:The N-methyl-d-aspartate (NMDA) receptor 2B gene (GRIN2B) was studied as a candidate gene of alcoholism. This study aimed to investigate the association between each of the three GRIN2B polymorphisms (rs1806201, rs1805247, and rs1805502) and alcoholism. This study included 206 alcoholic patients and 189 unrelated control subjects of Korean origin. Associations between genotype, allele, and haplotype frequencies of the polymorphisms and alcoholism were investigated. The genotype frequencies of rs1806201 and the haplotype analysis of SNPs in this study show significantly differences between the case and controls. These findings suggest new candidate SNPs in GRIN2B for studying the genetic susceptibility to alcoholism.
