Association between schizophrenia and the syntaxin 1A gene

Wong, Albert H.C.; Trakalo, Joseph; Likhodi, Olga; Yusuf, Muneeb; Macedo, António; Azevedo, M.H.; Klempan, Timothy A.; Pato, Michele T.; Honer, William G.; Pato, Carlos N.; Tol, Hubert H.M. Van; Kennedy, James L.

doi:10.1016/j.biopsych.2004.03.008

Cited by 40 publications

(33 citation statements)

References 29 publications

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“…SNAP-25 reduction was also observed in the hippocampi of patients with schizophrenia (Thompson et al, 2003). Singlenucleotide polymorphisms in syntaxin-1a associated with schizophrenia (Wong et al, 2004). SNARE complex assembly is impaired in human brain tissue from patients with AD and Parkinson's disease (Sharma et al, 2012).…”

Section: Fusion Machinerymentioning

confidence: 98%

Synaptic Vesicle-Recycling Machinery Components as Potential Therapeutic Targets

Kavalali

2017

Pharmacol Rev

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Section: Fusion Machinerymentioning

confidence: 98%

Synaptic Vesicle-Recycling Machinery Components as Potential Therapeutic Targets

Kavalali

2017

Pharmacol Rev

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“…Variation in the SNAP25 gene may increase the risk of schizophrenia, contributes to cognitive function in healthy subjects and patients with schizophrenia, is associated with metabolic measures in the hippocampus, antipsychotic treatment response, and with weight gain related to antipsychotic medications (Carroll et al, 2009;Corradini et al, 2009;Gosso et al, 2006;Muller et al, 2005;Musil et al, 2008;Scherk et al, 2008;Spellmann et al, 2008). Variation in STX1A (coding for syntaxin 1a) may be associated with a diagnosis of schizophrenia (Wong et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

A Novel Mechanism and Treatment Target for Presynaptic Abnormalities in Specific Striatal Regions in Schizophrenia

Barakauskas

Beasley

Barr

et al. 2010

Neuropsychopharmacol

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Abnormalities of amount and function of presynaptic terminals may have an important role in the mechanism of illness in schizophrenia. The SNARE proteins (SNAP-25, syntaxin, and VAMP) are enriched in presynaptic terminals, where they interact to form a functional complex to facilitate vesicle fusion. SNARE protein amounts are altered in the cortical regions in schizophrenia, but studies of proteinprotein interactions are limited. We extended these investigations to the striatal regions (such as the nucleus accumbens, ventromedial caudate (VMC), and dorsal caudate) relevant to disease symptoms. In addition to measuring SNARE protein levels, we studied SNARE protein-protein interactions using a novel ELISA method. The possible effect of antipsychotic treatment was investigated in parallel in the striatum of rodents that were administered haloperidol and clozapine. In schizophrenia samples, compared with controls, SNAP-25 was 32% lower (P ¼ 0.015) and syntaxin was 26% lower (P ¼ 0.006) in the VMC. In contrast, in the same region, SNARE protein-protein interactions were higher in schizophrenia (P ¼ 0.008). Confocal microscopy of schizophrenia and control VMC showed qualitatively similar SNARE protein immunostaining. Haloperidol treatment of rats increased levels of SNAP-25 (mean 24%, P ¼ 0.003), syntaxin (mean 18%, P ¼ 0.010), and VAMP (mean 16%, P ¼ 0.001), whereas clozapine increased only the VAMP level (mean 13%, P ¼ 0.004). Neither drug altered SNARE protein-protein interactions. These results indicate abnormalities of amount and interactions of proteins directly related to presynaptic function in the VMC in schizophrenia. SNARE proteins and their interactions may be a novel target for the development of therapeutics.

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“…Genotype duplicates concordance evaluation was performed by random (10% of the total screened) regenotyping and resulted in 100%. The SNP in exon 3 D68D T4C was analysed by PCR-RFPL with Hpy 99-I enzyme according to Wong et al 18 The À352…”

Section: Indices Of Insulin Secretion and Insulin Resistancementioning

confidence: 99%

Search for genetic variants of the SYNTAXIN 1A (STX1A) gene: the −352 A>T variant in the STX1A promoter associates with impaired glucose metabolism in an Italian obese population

et al. 2007

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Objective: To test if sequence variations of the SYNTAXIN 1A (STX1A) gene contribute to the susceptibility to type 2 diabetes in a cohort of overweight/obese subjects. Methods: A total of 717 overweight/obese individuals underwent oral glucose tolerance test and were stratified in four groups according to fasting and 2 h glucose levels (NGT, IGT, CGI, T2DM), representing the natural history of diabetes from normal glucose tolerance to overt disease. These subjects were analysed by a two-step genetic study. Functional analysis was performed by electrophoretic mobility shift assay (EMSA) and by supershift with CCAAT/enhancer-binding protein (C/EBP)b antibody. Results: Among the several sequence variations detected in the STX1A gene, the T allele of the À352 A4T single nucleotide polymorphism in the promoter was found in a lower frequency in the subset of individuals with greater impairment of insulin secretion (CGI). To confirm that a lower frequency of the T allele was associated with this condition, we genotyped a second group of 202 overweight/obese individuals with type 2 diabetes, and the frequency of the T allele was reduced in this group also (Po0.01). Logistic regression confirmed a protective odds ratio (0.49, Po0.01) for the T allele. The EMSA showed that the PRM À352 A allele binds transcription factors with lower affinity compared to the T allele, and incubation with C/EBPb antibody 'supershifted' the complex, indicating that C/EBPb had a different binding with the PRM À352T allele. Conclusion: A lower frequency of the PRM À352T allele of the STX1A gene was observed in overweight/obese subjects with impaired glucose regulation, particularly among individuals with combined glucose intolerance and overt diabetes. Both these groups have a greater defect in b-cell function compared to normal and glucose intolerant subjects, and this association together with the functional study suggests a possible role of the PRM À352 A4T variant in insulin secretion.

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Association between schizophrenia and the syntaxin 1A gene

Cited by 40 publications

References 29 publications

Synaptic Vesicle-Recycling Machinery Components as Potential Therapeutic Targets

Synaptic Vesicle-Recycling Machinery Components as Potential Therapeutic Targets

A Novel Mechanism and Treatment Target for Presynaptic Abnormalities in Specific Striatal Regions in Schizophrenia

Search for genetic variants of the SYNTAXIN 1A (STX1A) gene: the −352 A>T variant in the STX1A promoter associates with impaired glucose metabolism in an Italian obese population

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