title: SNAP-25 single nucleotide polymorphisms are associated with hyperactivity in autism spectrum disorders.
abstract: Synaptosomal-associated protein of 25kD (SNAP-25), a protein participating in the regulation of synaptic vesicle exocytosis and in calcium homeostasis, was recently involved in neuropsychiatric conditions. Because alterations affecting the homeostasis of calcium are described in patients affected by autism spectrum disorders (ASD) we investigated a possible involvement of SNAP-25 in ASD by evaluating five SNAP-25 gene polymorphisms in a cohort of 67 ASD children. Data analyzed in relationship with clinical outcomes and compared to those of 205 healthy sex-matched children did not reveal significant differences. Further analyses nevertheless showed the presence of highly significant associations of the rs363043 (CT) genotype, localized in the intron 1 region that affects the transcription factor binding sites of the SNAP-25 gene, with both increasing CARS (p=0.001) and hyperactivity scores (p=0.006). The finding that polymorphisms of the SNAP-25 gene, a gene involved in neurotransmission and regulation of calcium homeostasis, are associated with the degree of hyperactivity in children with ASD, reinforces the hypothesis that alterations of these mechanisms play a pivotal role in the events leading to ASD-associated behavioral impairment. Modulation of these processes could result in novel therapeutic strategies.
authors.affiliation: Don C. Gnocchi Foundation ONLUS, P. le Morandi 6, 20121 Milano, Italy. fguerini@dongnocchi.it
authors.forename: Franca R
authors.initials: FR
authors.lastname: Guerini
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Bolognesi
authors.forename: Matteo
authors.initials: M
authors.lastname: Chiappedi
authors.forename: Salvatorica
authors.initials: S
authors.lastname: Manca
authors.forename: Alessandro
authors.initials: A
authors.lastname: Ghezzo
authors.forename: Cristina
authors.initials: C
authors.lastname: Agliardi
authors.forename: Stefano
authors.initials: S
authors.lastname: Sotgiu
authors.forename: Sonia
authors.initials: S
authors.lastname: Usai
authors.forename: Michela
authors.initials: M
authors.lastname: Matteoli
authors.forename: Mario
authors.initials: M
authors.lastname: Clerici
mesh_terms: D000293:Adolescent; D002118:Calcium / Q000378:metabolism; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D050825:Synaptosomal-Associated Protein 25 / Q000235:genetics*
chemical_list: D050825:Synaptosomal-Associated Protein 25; D002118:Calcium