Identification of DNA variants in the SNAP-25 gene and linkage study of these polymorphisms and attention-deficit hyperactivity disorder

Barr, Cathy L.; Feng, Yu; Wigg, Karen; Bloom, Stacey; Roberts, Wendy; Malone, Molly; Schachar, Russell; Tannock, Rosemary; Kennedy, James L.

doi:10.1038/sj.mp.4000733

Cited by 194 publications

(162 citation statements)

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“…16,[44][45][46] A high comorbidity has been reported between ADHD and BD, more specifically with early-onset BD. 47 Therefore, our results suggest that SNAP25 might be a common susceptibility factors for these psychiatric disorders.…”

Section: Discussionmentioning

confidence: 99%

“…14,15 Third, SNAP25 gene has been widely associated with attention-deficit hyperactivity disorder (ADHD), which is known to share genetic susceptibility with early-onset BD. [16][17][18] We analysed SNAP25 as a candidate gene for susceptibility to BD and, more specifically, to earlyonset BD. We screened this gene for mutations and performed a case-control association study taking into account the AAO of the disease.…”

Section: Introductionmentioning

confidence: 99%

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A SNAP25 promoter variant is associated with early-onset bipolar disorder and a high expression level in brain

et al. 2009

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Bipolar disorder (BD) is one of the most common and persistent psychiatric disorders. Earlyonset BD has been shown to be the most severe and familial form. We recently carried out a whole-genome linkage analysis on sibpairs affected by early-onset BD and showed that the 20p12 region was more frequently shared in our families than expected by chance. The synaptosomal-associated protein SNAP25 is a presynaptic plasma membrane protein essential for the triggering of vesicular fusion and neurotransmitter release, and for which abnormal protein levels have been reported in postmortem studies of bipolar patients. We hypothesised that variations in the gene encoding SNAP25, located on chromosome 20p12, might influence the susceptibility to early-onset BD. We screened SNAP25 for mutations and performed a case-control association study in 197 patients with early-onset BD, 202 patients with late-onset BD and 136 unaffected subjects. In addition, we analysed the expression level of the two SNAP25 isoforms in 60 brains. We showed that one variant, located in the promoter region, was associated with early-onset BD but not with the late-onset subgroup. In addition, individuals homozygous for this variant showed a significant higher SNAP25b expression level in prefrontal cortex. These results show that variations in SNAP25, associated with an increased gene expression level in prefrontal cortex, might predispose to early-onset BD. Further analyses of this gene, as well as analysis of genes encoding for the SNAP25 protein partners, are required to understand the impact of such molecular mechanisms in BD.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A SNAP25 promoter variant is associated with early-onset bipolar disorder and a high expression level in brain

et al. 2009

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“…This results in two possible bands; one at 261bp (T) and one at 228bp (C). After gel electrophoresis, genotypes were scored as T/T homozygote, T/C heterozygote or C/C homozygote as described [Barr et al, 2000].…”

Section: Methodsmentioning

confidence: 99%

“…A mutant mouse, Coloboma, carrying a deletion of this gene shows high levels of hyperactivity [Wilson et al, 2000] and disruptions of dopaminergic signaling [Jones et al, 2001]. Gene association studies have related allelic variants of SNAP25 with attention deficit hyperactivity disorder (ADHD) [Brophy et al, 2002;Mill et al, 2002;Barr et al, 2000]. Although there is no formal evidence supporting a synaptogenesis deficit in ADHD, diminished brain volumes have been reported [Castellanos et al, 2002].…”

Section: Molecular Genetic Studies On Snap25 and Its Potential Role Imentioning

confidence: 99%

Synaptogenesis and heritable aspects of executive attention

Fossella

Sommer

Fan

et al. 2003

Ment. Retard. Dev. Disabil. Res. Rev.

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In humans, changes in brain structure and function can be measured non-invasively during postnatal development. In animals, advanced optical imaging measures can track the formation of synapses during learning and behavior. With the recent progress in these technologies, it is appropriate to begin to assess how the physiological processes of synapse, circuit, and neural network formation relate to the process of cognitive development. Of particular interest is the development of executive function, which develops more gradually in humans. One approach that has shown promise is molecular genetics. The completion of the human genome project and the human genome diversity project make it straightforward to ask whether variation in a particular gene correlates with variation in behavior, brain structure, brain activity, or all of the above. Strategies that unify the wealth of biochemical knowledge pertaining to synapse formation with the functional measures of brain structure and activity may lead to new insights in developmental cognitive psychology.

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“…For example, SNAP-25 has been shown to negatively regulate VGCCs in glutamatergic but not in GABAergic neurons [6]. A secondary regulatory function of SNAP-25 is also supported by its genetic association with synaptic abnormalities such as schizophrenia and attention deficit hyperactivity disorder (ADHD) in humans [7]. SNAP-25 expression is reduced twofold in the hippocampus and frontal lobe from schizophrenic patients [8] and in animal models for ADHD [9].…”

mentioning

confidence: 99%

A dual role of SNAP‐25 as carrier and guardian of synaptic transmission

Kochlamazashvili

Haucke

2013

EMBO Reports

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EMBO reports VOL 14 | NO 7 | 2013 579 hot off the press hot off the press C ontrol of exocytotic neurotransmitter release is essential for communication in the nervous system and for preventing synaptic abnormalities. The function of synaptosomal-associated protein of 25 kDa (SNAP-25) as a crucial component of the core machinery required for synaptic vesicle fusion is well established, but evidence is growing to suggest an additional modulatory role in neurotransmission. In this issue of EMBO reports, Antonucci et al show that the efficacy of evoked glutamate release is modulated by the expression levels of SNAP-25-a function that might relate to the ability of SNAP-25 to modulate voltage-gated calcium channels and presynaptic calcium ion concentration [1]. Altered synaptic transmission and short-term plasticity due to changes in SNAP-25 expression might have direct consequences for brain function and for the development of neuropsychiatric disorders.Communication between neurons is essential for brain function and occurs through chemical neurotransmission at specialized cell-cell contacts termed 'synapses'. Within the nerve terminal of the presynaptic neuron electrical stimuli cause the opening of voltage-gated calcium channels (VGCCs), which results in the influx of calcium ions. This triggers the exocytic release of neurotransmitter by fusion of synaptic vesicles with the presynaptic membrane. Released neurotransmitter molecules are detected by specific receptors expressed by the postsynaptic neuron.Calcium-induced synaptic vesicle fusion requires complex assembly between the soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein receptor (SNARE) synaptobrevin 2, located on the synaptic vesicle, and the abundant plasma membrane SNAREs SNAP-25 and syntaxin 1, on the opposing presynaptic plasma membrane. SNARE complex assembly is tightly regulated by Sec1/Munc18-like proteins [2]. Further regulatory factors such as the synaptic vesicle calcium-sensing protein synaptotagmin 1 couple the SNARE machinery to presynaptic calcium influx. SNARE-mediated neuro transmitter release occurs preferentially at the active zone-a presynaptic membrane domain specialized for exocytosis within which VGCCs are positioned close to docked synaptic vesicles through a proteinaceous cytomatrix and associated cell adhesion molecules [3,4].An unresolved conundrum in synaptic transmission remains-the observation that SNARE proteins, such as SNAP-25, are among the most highly expressed, in copy number, presynaptic proteins, whilst only a handful of SNARE complexes are needed to drive the fusion of a single synaptic vesicle [5]. Why, then, are SNAREs such as SNAP-25 so abundant? One possible explanation might be that SNARE proteins, in addition to forming trans-SNARE complexes, assemble with other proteins, and such partitioning might regulate neurotransmission. For example, SNAP-25 has been shown to negatively regulate VGCCs in glutamatergic but not in GABAergic neurons [6]. A secondary regulatory function of SNAP-25 is also su...

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Identification of DNA variants in the SNAP-25 gene and linkage study of these polymorphisms and attention-deficit hyperactivity disorder

Cited by 194 publications

References 19 publications

A SNAP25 promoter variant is associated with early-onset bipolar disorder and a high expression level in brain

A SNAP25 promoter variant is associated with early-onset bipolar disorder and a high expression level in brain

Synaptogenesis and heritable aspects of executive attention

A dual role of SNAP‐25 as carrier and guardian of synaptic transmission

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