SNAP-25 single nucleotide polymorphisms are associated with hyperactivity in autism spectrum disorders

Guerini, Franca Rosa; Bolognesi, Elisabetta; Chiappedi, Matteo; Manca, Salvatorica; Ghezzo, Alessandro; Agliardi, Cristina; Sotgiu, Stefano; Usai, Sonia; Matteoli, Michela; Clerici, Mario

doi:10.1016/j.phrs.2011.03.015

Cited by 63 publications

(53 citation statements)

References 34 publications

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“…Previous studies have revealed changes in RIM3 expression levels in schizophrenia [63,64]. In addition, several studies have suggested that functional mutations in genes encoding VDCCs can lead to autism, and SNAP-25 single nucleotide polymorphisms are associated with autism [59][60][61]65]. These reports further suggest that synaptic dysfunction through RIM3 functional abnormalities in Ca 2+ regulation may be relevant for the pathogenesis underlying neurodevelopmental disorders such as autism.…”

Section: Discussionmentioning

confidence: 93%

Rab3 interacting molecule 3 mutations associated with autism alter regulation of voltage-dependent Ca2+ channels

et al. 2015

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Section: Discussionmentioning

confidence: 93%

Rab3 interacting molecule 3 mutations associated with autism alter regulation of voltage-dependent Ca2+ channels

et al. 2015

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“…The study by Guerini et al (2011b) showed that singlenucleotide polymorphisms (SNPs) of the synaptosomalassociated protein of 25-kDa gene are associated with hyperactivity in ASD. Results of a family-based linkage study found that HLA polymorphisms were associated with ASD in Italian children (Guerini et al, 2011a).…”

Section: Discussionmentioning

confidence: 99%

Methylenetetrahydrofolate Reductase Polymorphisms C677T and Risk of Autism in the Chinese Han Population

Guo

Chen²,

Liu³

et al. 2012

Genetic Testing and Molecular Biomarkers

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Causes of autism are still unknown. Some studies have shown that autism might be associated with metabolic abnormalities in the folate/homocysteine pathway, which is involved in DNA methylation, thus altering gene expression. The association between the methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphisms and the risk of autism is still controversial and ambiguous. The purpose of this study was to examine the effect of the MTHFR C677T polymorphism on the autism risk in the Chinese Han population. A population-based case-control study was conducted in 186 children with autism and 186 controls. The MTHFR C677T polymorphisms were determined by using a polymerase chain reaction-restriction fragment length polymorphism assay. The frequency of genotype MTHFR 677TT in children with autism (16.1%) was significantly higher (odds ratio [OR]=2.04; 95% confidence interval [CI]=1.07, 3.89; p=0.03] than those in controls (8.6%). When stratifying by select-item scores on the Autism Diagnostic Interview-Revised, it was found that children with current overactivity had a significantly higher frequency of the MTHFR 677TT genotype (OR=2.77, 95% CI=1.17, 6.60; p=0.02) than those without. This study suggested that MTHFR C677T is a risk factor of autism in Chinese Han children.

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“…In neurons, SNAP25 is located at the presynaptic plasma membrane where it also modulates the activity of voltage-gated calcium channels [8,39,58]. Polymorphisms in SNAP25 have been associated with different neuropsychiatric conditions such as ADHD (reviewed in [9]), schizophrenia, bipolar disorders, and autism [9,13,23], and variants in the gene were reported to modulate cognitive performances [19,20,45]. In particular, SNPs located in a *14 kb region in intron 1 were associated with the intelligence quotient (IQ) in Dutch cohorts [19,20].…”

Section: Introductionmentioning

confidence: 99%

Variants in SNAP25 are targets of natural selection and influence verbal performances in women

Cagliani

Riva

Marino

et al. 2011

Cell. Mol. Life Sci.

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Descriptions of genes that are adaptively evolving in humans and that carry polymorphisms with an effect on cognitive performances have been virtually absent. SNAP25 encodes a presynaptic protein with a role in regulation of neurotransmitter release. We analysed the intra-specific diversity along SNAP25 and identified a region in intron 1 that shows signatures of balancing selection in humans. The estimated TMRCA (time to the most recent common ancestor) of the SNAP25 haplotype phylogeny amounted to 2.08 million years. The balancing selection signature is not secondary to demographic events or to biased gene conversion, and encompasses rs363039. This SNP has previously been associated to cognitive performances with contrasting results in different populations. We analysed this variant in two Italian cohorts in different age ranges and observed a significant genotype effect for rs363039 on verbal performances in females alone. Post hoc analysis revealed that the effect is driven by differences between heterozygotes and both homozygous genotypes. Thus, heterozygote females for rs363039 display higher verbal performances compared to both homozygotes. This finding was replicated in a cohort of Italian subjects suffering from neuromuscular diseases that do not affect cognition. Heterozygote advantage is one of the possible reasons underlying the maintenance of genetic diversity in natural populations. The observation that heterozygotes for rs363039 display higher verbal abilities compared to homozygotes perfectly fits the underlying balancing selection model. Although caution should be used in inferring selective pressures from observed signatures, SNAP25 might represent the first description of an adaptively evolving gene with a role in cognition.

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SNAP-25 single nucleotide polymorphisms are associated with hyperactivity in autism spectrum disorders

Cited by 63 publications

References 34 publications

Rab3 interacting molecule 3 mutations associated with autism alter regulation of voltage-dependent Ca2+ channels

Rab3 interacting molecule 3 mutations associated with autism alter regulation of voltage-dependent Ca2+ channels

Methylenetetrahydrofolate Reductase Polymorphisms C677T and Risk of Autism in the Chinese Han Population

Variants in SNAP25 are targets of natural selection and influence verbal performances in women

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