engleski

Ser310Ala functional polymorphism in the GluR7 glutamate receptor subunit gene and alcohol dependence

Glutamate receptors, the major excitatory neurotransmitter receptors in the brain, have been implicated in acute and chronic effects of alcohol, including alcohol dependence and withdrawal. Kainate ionotropic glutamate receptors have emerged in recent years as important targets of alcohol’s action in the central nervous system. The GRIK3 gene, encoding GluR7 subunit of kainate receptors, is localized on chromosome 1, close to a region associated with alcoholism and alcoholism-related phenotypes. However, diverse results obtained regarding the association of GRIK3 gene with alcoholism might be due to the heterogeneity in alcoholism etiology and phenotype characteristics. Hence, the aim of this study was to investigate the role of the GRIK3 functional polymorphism in patients with alcoholism subdivided according to early/late onset of alcohol abuse, the presence/absence of aggressive behavior and suicide attempts. Genotyping of Ser310Ala polymorphism (rs6691840) in the GRIK3 gene was performed in 275 alcohol-dependent patients of both genders and different smoking status, by using TaqMan Real-Time allelic discrimination after DNA extraction from the blood. The distribution of genotypes and alleles did not differ significantly in alcohol-dependent patients stratified by gender, smoking status, aggressive behavior or suicide attempts. However, the results demonstrated that alcohol-dependent patients with late onset had a higher frequency of a homozygous CC genotype than patients with the early onset of alcohol abuse often reflecting greater alcoholism severity, higher risk for recurrence, as well as comorbid antisocial personality disorder and conduct disorder. Additional studies are needed to further investigate the role of GRIK3 gene in the development of alcoholism.

alcoholism; alcoholism-related phenotypes; GRIK3 gene; polymorphism; glutamate

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