Complexo SNARE na susceptibilidade ao transtorno por uso de álcool

Abstract

Background: The etiology of Alcohol Dependence is multifactorial, resulting from the interplay of environmental and genetic factors, including variants in neurotransmission related genes. In this sense, the Soluble NSF-Attachment Protein Receptors (SNARE) complex, which acts on neurotransmitter release, could play an important role in this disorder. The aim of the present study was to evaluate polymorphisms in SNARE complex genes (STX1A rs2228607; SYT1 rs1880867 and rs2251214; VAMP2 26 bp Ins/Del; SNAP25 rs6108461 and rs8636) in relation to Alcohol Dependence susceptibility. Methods: The sample comprised 115 men under inpatient treatment for with Alcohol Dependence and 308 non-dependent controls. Additionally, 278 men with Attention-Deficit/Hyperactivity Disorder (ADHD), of which 35 presented comorbidity with Alcohol Dependence were subsequently evaluated in order to replicate the association. Results: A nominal association was found between the VAMP2 26 bp Ins/Del polymorphism and susceptibility to Alcohol Dependence, where the Ins/Ins genotype showed a risk to this disorder (p = 0.012; OR = 2.21). This result was supported by the ADHD replication sample, where the Ins/Ins genotype was also more frequent among Alcohol Dependent cases (p = 0.008; OR = 5.26). Other polymorphisms and haplotype analyses did not reveal significant differences between cases and controls. Conclusion: Overall, the present study suggests that VAMP2 26 bp Ins/Del polymorphism, previously associated with ADHD, is also implicated in Alcohol Dependence susceptibility.