The Association of SNAP25 Gene Polymorphisms in Attention Deficit/Hyperactivity Disorder: a Systematic Review and Meta-Analysis

Abstract

Attention deficit/hyperactivity disorder (ADHD) is one of the most highly heritable psychiatric disorders in childhood. The risk gene mutation accounts for about 60 to 90 % cases. Synaptosomal-associated protein of 25 kDa (SNAP-25) is a presynaptic plasma membrane protein which is expressed highly and specifically in the neuronal cells. A number of evidences have suggested the role of SNAP-25 in the etiology of ADHD. Notably, the animal model of coloboma mouse mutant bears a ∼2-cM deletion encompassing genes including SNAP25 and displays spontaneous hyperkinetic behavior. Previous investigators have reported association between SNPs in SNAP25 and ADHD, and controversial results were observed. In this study, we analyzed the possible association between six polymorphisms (rs3746544, rs363006, rs1051312, rs8636, rs362549, and rs362998) of SNAP25 and ADHD in a pooled sample of ten family-based studies and four case-control studies by using meta-analysis. The combined analysis results were significant only for rs3746544 (P = 0.010) with mild association (odds ratio (OR) = 1.14). And, the meta-analysis data for rs8636, rs362549, and rs362998 are the first time to be reported; however, no positive association was detected. In conclusion, we report some evidence supporting the association of SNAP25 to ADHD. Future research should emphasize genome-wide association studies in more specific subgroups and larger independent samples.

Emerging Synaptic Molecules as Candidates in the Etiology of Neurological Disorders

“…In a linkage study, two polymorphisms located in the 3′-untranslated region of the human SNAP gene were associated with ADHD [48]. Additional evidence for a role of SNAP25 in ADHD was provided by a recent meta-analysis [49]. In SCZ, the structure of the hippocampus is abnormal, and a decrease in the amount of SNAP25 has been observed in the hippocampus and areas of the cortex of patients with this disease [44, 46, 47].…”

Peer Review #3 of "Genetic influences on creativity: an exploration of convergent and divergent thinking (v0.1)"

“…The product of SNAP25, a presynaptic plasma membrane protein, is a key protein for the docking and fusion of synaptic and other vesicles (Veit Michael, Söllner Thomas H. & Rothman James E., 1996). It is suggested that high levels of expression of this gene in specific areas of the adult brain are related to nerve terminal plasticity (Oyler et al, 1989;Osen-Sand et al, 1993 Manuscript to be reviewed disorder (Liu et al, 2017). Since creativity is a complex cognitive process, these discoveries provided hints for the relation between rs362584 and creativity.…”

Environmental and Genetic Influences in Attention Deficit Hyperactivity Disorder (ADHD) and its Comorbidities

“…Studies on childhood ADHD on the role of dopaminergic and serotonergic genes as well as genes involved in synaptic plasticity (107,138), have repeatedly been replicated, although effect sizes are small. Other studies, such as recent meta-analysis, involve SNAP-25 (a cellular calcium modulator) polymorphism (139). Candidate gene studies identified both similarities and differences between genetics of childhood and adult ADHD (12).…”