INTRODUCTION
The etiology of attention deficit hyperactivity disorder (ADHD) is not completely understood, but it is well known that the genetic transmission is an important factor in ADHD etiology.1 In particular, it is supposed to be a complex psychiatric disorder which also involves the interaction of gene and environment.2 Despite the studies reporting association between ADHD and serotonergic system, genes of dopaminergic system are the mostly blamed system genes among the genetic factors.3,4 However, recently, researchers suppose that the problem at the synaptic gap is not only limited to the dopamine, but also there may be problems in the modulation of neurotransmitter releasing and synaptogenesis, and they targetted their efforts towards the genes encoding presynaptic proteins having roles in those processes.5
Vesicle-associated membrane protein 2 (VAMP2) (synaptobrevin 2) and syntaxin 1A along with The synaptosomal-associated protein, 25 kDa (SNAP-25) protein compose SNARE proteins that have roles in the modulation of neurotransmitter releasing.6 Among these genes, the most frequently studied one is SNAP-25 gene and the relation between ADHD and two polymorphisms of (MnlI, DdeI) this gene was investigated in many studies. A relation between either or both DdeI and MnlI polymorphisms are found to be related with ADHD.7-9 A relation between ADHD and SNAP-25 MnlI polymorphism was determined in a study which was performed in our country, Turkey.10 In another study from Turkey, the changes in the brain bloodstream with single dose of psychostimulant in ADHD subjects were analyzed and they reported that brain bloodstream may be affected by SNAP-25 polymorphism after psychostimulant therapy.11 All these studies have brought up the other proteins that have roles in the same function along with SNAP-25. However, no study was noticed investigating the relation between VAMP2 and syntaxin 1A genes and ADHD in the literature. Yet, there are some studies investigating the relation between VAMP2 and syntaxin 1A genes and various psychiatric disorders that the modulation of neurotransmitter releasing is important in their etiopathogenesis.
No relation was obtained between the gene polymorphisms of SNARE proteins; VAMP2, syntaxin 1A and SNAP-25 and schizophrenia.12 No relation was obtained between VAMP2 gene and bipolar disease, which has a comorbid diagnosis rate of 9.5% with ADHD, in a study that was performed among bipolar patients.13,14
While no relation was determined between schizophrenia and exon 3 polymorphism of syntaxin 1A gene, a relation was reported between schizophrenia and intron 7 T>C polymorphism of syntaxin 1A gene.15 In the post-mortem brain studies of the schizophrenia patients, higher levels of syntaxin 1A in cingulat cortices and higher levels of syntaxin 1A m-RNA in temporal cortices with respect to the control subjects were determined.16,17 Bartl et al.18 reported that they observed reduction in the syntaxin 1A m-RNA levels and down-regulation in synaptic proteins after administration of methylphenidate (MPH) in a study which they have investigated the effects of MPH, currently used in the treatment of ADHD.
In this study, we aimed to investigate the relation between VAMP-2 and syntaxin 1A genes, which have roles in encoding presynaptic proteins, and ADHD.