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Vitamin D is endowed with a number of biological properties, including down-regulation of inflammation, and might contribute to the pathogenesis of autism spectrum disorders (ASD). Vitamin D binds to the vitamin D Receptor (VDR); the biological activity of the ensuing complex depends on VDR FokI, BsmI, ApaI, and TaqI gene polymorphisms. We evaluated such Single Nucletoide Polymorphismsm (SNPs) in a cohort of 100 Italian families with ASD children. FokI genotype distribution was skewed in ASD children compared with their healthy sibs (Pc = 0.03 2 df) and to a group of 170 Italian healthy women (HC) (Pc = 0.04 2 df). FokI genotype and allelic distribution skewing were also observed in mothers of ASD children compared to HC (Pc = 0.04 2 df). Both Transmission Disequilibrium Test for single loci and haplotype analysis distribution revealed a major FokI (C) allele-mediated protective effect, which was more frequently transmitted (73%) than not transmitted to healthy sibs (P = 0.02). A protective FokI-, BsmI-, ApaI-, and TaqI (CCAG) haplotype was more frequently carried by healthy sibs than by ASD children (P = 1 × 10-4 ; OR: 0.1, 95% CI: 0.03-0.4) too. Finally, a strong gene-dose association of FokI (T) allele with both higher Childhood Autism Rating Scale score (Pc = 0.01) and, particularly, with hyperactivity behavior (Pc = 0.006) emerged in ASD children. Because the protein produced by the FokI (T) allele is transcriptionally less active than that produced by the FokI (C) allele, the reduced biological activity of the vitamin D/VDR complex prevalent in ASD could favor ASD- and maternal immune activation- associated inflammation. Vitamin D supplementation might be useful in preventative and rehabilitation protocols for ASD. LAY SUMMARY: Vitamin D deficiency and Vitamin D receptor (VDR) polymorphisms are associated with structural and functional brain abnormalities and behavioral disorders. We analyzed the association of VDR gene polymorphisms in a cohort of 100 Italian

This case-control study involved a total of 29 autistic children (Au) aged 6 to 12 years, and 28 gender and age-matched typically developing children (TD). We evaluated a high number of peripheral oxidative stress parameters, erythrocyte and lymphocyte membrane functional features and membrane lipid composition of erythrocyte. Erythrocyte TBARS, Peroxiredoxin II, Protein Carbonyl Groups and urinary HEL and isoprostane levels were elevated in AU (confirming an imbalance of the redox status of Au); other oxidative stress markers or associated parameters (urinary 8-oxo-dG, plasma Total antioxidant capacity and plasma carbonyl groups, erythrocyte SOD and catalase activities) were unchanged, whilst peroxiredoxin I showed a trend of elevated levels in red blood cells of Au children. A very significant reduction of both erythrocyte and lymphocyte Na+, K+-ATPase activity (NKA), a reduction of erythrocyte membrane fluidity, a reduction of phospatydyl serine exposition on erythrocyte membranes, an alteration in erythrocyte fatty acid membrane profile (increase in MUFA and in ω6/ω3 ratio due to decrease in EPA and DHA) and a reduction of cholesterol content of erythrocyte membrane were found in Au compared to TD, without change in erythrocyte membrane sialic acid content and in lymphocyte membrane fluidity. Some Au clinical features appear to be correlated with these findings; in particular, hyperactivity score appears to be related with some parameters of the lipidomic profile and membrane fluidity, and ADOS and CARS score are inversely related to peroxiredoxin II levels. Oxidative stress and erythrocyte structural and functional alterations may play a role in the pathogenesis of Autism Spectrum Disorders and could be potentially utilized as peripheral biomarkers.

Synaptosomal-associated protein of 25 KD (SNAP-25) is a protein that participates in synaptic vesicle exocytosis through the formation of a SNARE complex; SNAP-25 also plays a pivotal role in modulating calcium homeostasis through negative regulation of voltage-gated calcium channels. SNAP-25 has been involved in different neuropsychiatric disorders, including attention deficit hyperactivity disorder. There are well known physiological gender differences in many neuropsychological skills, and there are even more striking gender differences in patients with attention deficit hyperactivity disorder and autism spectrum disorders. We hypothesize that these differences are the result of a mechanism involving SNAP-25 polymorphisms and its differential expression in specific brain areas.

Synaptosomal-associated protein of 25 KD (SNAP-25) is a protein that participates in synaptic vesicle exocytosis through the formation of a SNARE complex; SNAP-25 also plays a pivotal role in modulating calcium homeostasis through negative regulation of voltage-gated calcium channels. SNAP-25 has been involved in different neuropsychiatric disorders, including attention deficit hyperactivity disorder. There are well known physiological gender differences in many neuropsychological skills, and there are even more striking gender differences in patients with attention deficit hyperactivity disorder and autism spectrum disorders. We hypothesize that these differences are the result of a mechanism involving SNAP-25 polymorphisms and its differential expression in specific brain areas.

Synaptosomal-associated protein of 25 KD (SNAP-25) is a protein that participates in synaptic vesicle exocytosis through the formation of a SNARE complex; SNAP-25 also plays a pivotal role in modulating calcium homeostasis through negative regulation of voltage-gated calcium channels. SNAP-25 has been involved in different neuropsychiatric disorders, including attention deficit hyperactivity disorder. There are well known physiological gender differences in many neuropsychological skills, and there are even more striking gender differences in patients with attention deficit hyperactivity disorder and autism spectrum disorders. We hypothesize that these differences are the result of a mechanism involving SNAP-25 polymorphisms and its differential expression in specific brain areas.

Synaptosomal-associated protein of 25 KD (SNAP-25) is a protein that participates in synaptic vesicle exocytosis through the formation of a SNARE complex; SNAP-25 also plays a pivotal role in modulating calcium homeostasis through negative regulation of voltage-gated calcium channels. SNAP-25 has been involved in different neuropsychiatric disorders, including attention deficit hyperactivity disorder. There are well known physiological gender differences in many neuropsychological skills, and there are even more striking gender differences in patients with attention deficit hyperactivity disorder and autism spectrum disorders. We hypothesize that these differences are the result of a mechanism involving SNAP-25 polymorphisms and its differential expression in specific brain areas.