Association of tumor necrosis factor alpha gene -G308A polymorphism with schizophrenia

Schwab, Sibylle G.; Mondabon, Stephanie; Knapp, Michael; Albus, Margot; Hallmayer, Joachim; Borrmann-Hassenbach, Margitta; Trixler, M.; Groβ, Magdalena; Schulze, Thomas G.; Rietschel, Marcella; Lerer, Bernard; Maier, Wolfgang; Wildenauer, Dieter B.

doi:10.1016/s0920-9964(02)00534-0

Cited by 51 publications

(40 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Studies have shown that G308A polymorphisms of TNF gene is possibly involved in the aetiology of schizophrenia [124][125][126]. Furthermore, TNF is located on the short arm of chromosome 6 (6p21.1-21.3), a locus that is modulating the predisposition to schizophrenia [127,128].…”

Section: Modelmentioning

confidence: 99%

Tumour necrosis factor - alpha mediated mechanisms of cognitive dysfunction

Baune

Camara²,

Eyre³

et al. 2012

Translational Neuroscience

View full text Add to dashboard Cite

Background: Tumour necrosis factor -alpha (TNF-α) is a pro-inflammatory cytokine that combines a plethora of activities in the early stages of an immune response. TNF-α has gained increasing importance given TNF-α upregulation in multiple brain pathologies like neuropsychiatric conditions such as depression, schizophrenia, as well as neuroinflammatory disorder like multiple sclerosis (MS). Aim: The aim of this review is to critically analyse neurobiological, immunological and molecular mechanisms through which TNF-α influences the development of cognitive dysfunction. Principal findings/results: The review presents several lines of original research showing that the immunological properties of TNF-α exacerbate inflammatory responses in the central nervous system such as microglial and endothelial activation, lymphocytic and monocytic infiltration and the expression of downstream pro-inflammatory cytokines and apoptotic factors. Depression, schizophrenia, and MS all manifest symptoms of activated immune response along with cognitive dysfunction, with TNF-α overexpression as a central clinical feature common to these disorders. Furthermore, TNF-α acts negatively on neuroplasticity and the molecular mechanisms of memory and learning (i.e., long-term potentiation and long-term depression). TNF-α also exerts influence over the production of neurotrophins (i.e., nerve growth factor and brain-derived neurotrophic factor), neurogenesis, and dendritic branching. Conclusions/significance: This review outlines that TNF-α and its receptors have a substantial yet underappreciated influence on the development and progression of neuropsychiatric symptoms across several disease entities. An improved understanding of these underlying mechanisms may help develop novel therapeutic targets in the form of drugs specifically targeting downstream products of TNF-α activation within the central nervous system.

show abstract

Section: Modelmentioning

confidence: 99%

Tumour necrosis factor - alpha mediated mechanisms of cognitive dysfunction

Baune

Camara²,

Eyre³

et al. 2012

Translational Neuroscience

View full text Add to dashboard Cite

show abstract

“…39 The physiological role of type II kinases is not well defined yet, but they may be involved in tumour necrosis factor (TNF)a-mediated signalling. 66 Interestingly, there are some reports on association of SNPs in the TNFa gene with schizophrenia, 67,68 suggesting that impairment of TNFa-mediated signalling may contribute to development of schizophrenia. Moreover, there are also reports on a possible involvement of PIP5K2A in the regulation of gene expression, pre-mRNA processing and mRNA transport in general.…”

Section: -36mentioning

confidence: 99%

Evidence for association of DNA sequence variants in the phosphatidylinositol-4-phosphate 5-kinase IIα gene (PIP5K2A) with schizophrenia

et al. 2006

View full text Add to dashboard Cite

Linkage studies in schizophrenia have identified a candidate region on chromosome 10p14-11 as reported for several independent samples. We investigated association of DNA sequence variants in a plausible candidate gene located in this region, the gene for phosphatidylinositol-4-phosphate 5-kinase IIa (PIP5K2A), in a sample of 65 sib-pair families for which linkage had been reported. Evidence for association was obtained for 15 polymorphisms spanning 73.6 kb in the genomic region of the gene between intron 4 and the 3 0 untranslated region, a region with high degree of linkage disequilibrium. Single nucleotide polymorphism (SNP) rs10828317 located in exon 7 and causing a non-synonymous amino-acid exchange (asparagine/serine) produced a P-value of 0.001 (experiment-wide significance level 0.00275) for over-transmission of the major allele coding for serine, analysed by transmission disequilibrium test using FAMHAP. Association of this SNP with schizophrenia has been also described in a sample of 273 Dutch schizophrenic patients and 580 controls (P = 0.0004). PIP5K2A is involved in the biosynthesis of phosphatidylinositol-4,5-bisphosphate (PI(4,5)P 2 ), one of the key metabolic crossroads in phosphoinositide signalling. PI(4,5)P 2 plays a role in membrane transduction of neurotransmitter signals as well as in intracellular signalling, pathways that may be impaired in schizophrenia.

show abstract

“…Several gene loci in this region have been found to be putatively associated with schizophrenia. These are dysbindin 1 (DTNBP1, 6p22.3), 3 myelin oligodendrocyte glycoprotein (MOG, 6p22.1), 4 tumour necrosis factor alpha (TNF-a, 6p21.3), [5][6][7] the notch type-4 receptor (NOTCH4, 6p21.3) [8][9][10][11][12] and tenascin B (TNXB, 6p21.3). 13 Among these, DTNBP1 is the gene most consistently replicated and, positive findings have been obtained in independent data sets; albeit no single haplotype having been shown to be in common across all the samples.…”

Section: Introductionmentioning

confidence: 99%

The discoidin domain receptor 1 as a novel susceptibility gene for schizophrenia

et al. 2007

View full text Add to dashboard Cite

Evidence suggests that myelin alterations could predispose to schizophrenia. Reduced expression of several myelin genes has been observed in schizophrenia patients. Recently, we identified the discoidin domain receptor 1 (DDR1; located at human chromosome 6p21.3) as a myelin gene in the mouse model and in a human oligodendroglial cell line. In the present study we screened for single nucleotide polymorphisms (SNPs) in the DNA from 100 schizophrenia patients. We identified a novel mutation within exon 10 that produces the amino-acid substitution N502S in the a-d isoforms, and M475V in the e isoform. However the frequency of the mutation (2%) was similar in schizophrenia patients and in control subjects. In a casecontrol assessment with 389 schizophrenic patients and 615 controls, we identified one SNP (SNP9, rs1049623) associated with schizophrenia (odds ratio = 1.44, 95% confidence interval: 1.15-1.79, adjusted P = 0.0016). This association was confirmed in haplotype analysis; the SNPs 9-10-11 (rs1049623, rs2267641 and rs2239518) haplotype remaining significant even after adjustment for multiple testing (adjusted P = 0.0136). Of note was a strong gender dependence in the association, that is, statistical significance restricted to men (adjusted P-value = 0.0002). Regression analysis of DDR1 mRNA expression in peripheral blood lymphocytes from schizophrenia patients showed that the presence of the G allele significantly decreased the relative number of mRNA copies in a dose-dependent manner (P = 0.003). These data suggest that the risk haplotype tags a cis-acting variant involved in the transcription regulation system of the gene. In conclusion, we propose the DDR1 as a new susceptibility gene for schizophrenia.

show abstract

Association of tumor necrosis factor alpha gene -G308A polymorphism with schizophrenia

Cited by 51 publications

References 37 publications

Tumour necrosis factor - alpha mediated mechanisms of cognitive dysfunction

Tumour necrosis factor - alpha mediated mechanisms of cognitive dysfunction

Evidence for association of DNA sequence variants in the phosphatidylinositol-4-phosphate 5-kinase IIα gene (PIP5K2A) with schizophrenia

The discoidin domain receptor 1 as a novel susceptibility gene for schizophrenia

Contact Info

Product

Resources

About