Synaptosomal-associated protein 25 (SNAP-25) and attention deficit hyperactivity disorder (ADHD): evidence of linkage and association in the Irish population

Several lines of evidence have suggested that ADHD is a polygenic disorder produced by the interaction of several genes each of a minor effect. Synaptosomal-associated protein 25 (SNAP-25) is a presynaptic plasma membrane protein which is expressed highly and specifically in the nerve cells. The gene encodes a protein essential for synaptic vesicle fusion and neurotransmitter release. Animal model studies showed that the coloboma mouse mutant has a hyperactive phenotype similar to that of ADHD. The hyperactive phenotype of this model has been shown to be the result of a deletion of the SNAP-25 gene. DNA variations within or closely mapped to the SNAP-25 gene may alter the level of expression and hence may have an effect on the function of synaptic vesicle fusion and neurotransmitter release. Using HHRR and TDT we analysed 93 ADHD nuclear families from Ireland and found increased preferential transmission of SNAP-25/DdeI allelel to ADHD cases; HHRR (chi(2) = 6.55, P = 0.01) and linkage (TDT) (chi(2) = 6.5, P = 0.015). In contrast to our findings, Barr et al(1) reported an increased transmission of allele 2 of the DdeI polymorphism though this was not statistically significant. However, they also reported a significantly increased transmission of a haplotype (made of allele 1 of MnlI and allele 2 of the DdeI) in their Canadian ADHD sample. It is not clear what the role of SNAP-25 in ADHD is until these findings are either confirmed or refuted in other ADHD samples.