engleski

The association of GRIK3 polymorphism with alcoholism in the subjects of Croatian origin

Alcoholism is frequent and complex chronic disorder with numerous genetic and environmental risk factors. Genetic vulnerability to alcohol dependence is likely due to multiple contributing genes encoding proteins in many neurotransmitter systems and signal transduction pathways. Glutamatergic system has been implicated in acute and chronic effects of alcohol and represents a potential target for development of promising novel alcoholism therapeutics. In recent years, kainate ionotropic glutamate receptors have emerged as important targets of alcohol’s action in the brain. Namely, some reports suggested that Ser310Ala polymorphism in the GRIK3 gene, encoding the GluR7 subunit of kainate receptors, is associated with alcoholism. However, the fact that other studies failed to demonstrate these findings, might be explained by the differences in the origin of participants, as the role of genetic and environmental risk factors may be different in various populations. Hence, the aim of this study was to examine the allelic and genotypic association of GRIK3 functional polymorphism with alcohol dependence in subjects of Croatian origin. A total of 483 unrelated Caucasian subjects of Croatian origin, including 208 healthy control subjects and 275 patients diagnosed with alcohol dependence (DSM-IV criteria), stratified according to gender, age and nicotine dependence, were enrolled in the study. Following DNA extraction from the whole blood, genotyping of Ser310Ala GRIK 3 polymorphism (rs6691840) was performed by using TaqMan Real-Time allelic discrimination technique. No significant differences in the frequency of the genotypes and alleles for rs6691840 between alcohol-dependent and control individuals were detected. Moreover, in order to define the alcohol-related phenotypes more specifically, alcohol-dependent participants were additionally subdivided according to the early/late onset of alcohol abuse, presence/absence of aggressive behavior and lifetime suicide attempts. Although the distribution of genotypes and alleles did not differ between alcohol-dependent patients stratified by aggressive behavior or suicide attempts, the results demonstrated significant differences in the frequency of a homozygous CC genotype between the alcohol-dependent patients with the early onset (before 25 years of age) and patients with the late onset (after 25 years of age) of alcohol abuse. Further research is necessary to elucidate the role of GRIK3 gene in the development of alcoholism.

Alcoholism; GRIK3 gene; GluR7 kainate glutamate receptor; polymorphism

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