engleski

The association of Ser310Ala functional polymorphism in the GluR7 glutamate receptor subunit gene with the age of onset of alcohol abuse in alcohol-dependent patients

There is accumulating data suggesting an involvement of glutamate in the acute and chronic effects of alcohol, including dependence and withdrawal, and glutamatergic system is emerging as potential target for alcoholism treatment. Recent studies have suggested an association of ionotropic glutamate receptor genes with alcohol dependence. The aim of this study was to examine the association of Ser310Ala functional polymorphism (rs6691840) in the GluR7 glutamate kainate receptor subunit gene (GRIK3) with the development of alcoholism. New insights into the genetic background of alcohol addiction could help identify individuals with high risk of alcoholism development, which would contribute to the prevention as well as alleviation of the consequences of this complex disorder. The study included 275 alcohol-dependent patients and 208 healthy subjects. Possible differences in the frequency of GRIK3 genotypes and alleles between subjects of different gender and smoking status, as well as between alcohol-dependent patients stratified according to aggressive and suicidal behavior, onset of alcohol abuse and type of alcoholism according to Cloninger’s classification were also studied. Genotyping of Ser310Ala polymorphism (rs6691840) in the GRIK3 gene was performed by using TaqMan Real-Time allelic discrimination technique after extraction of DNA from the whole blood with a salting out procedure. Allele and genotype frequencies in the control and alcohol-dependent subjects were compared using χ2 test. The results demonstrated lower frequency of homozygous CC genotype in patients who started abusing alcohol before 25. years of age in relation to alcohol-dependent subjects with the late onset of alcohol abuse. The results have provided supporting evidence for the association of the GRIK3 gene polymorphism (rs6691840) with the age of onset of alcohol abuse in patients of Croatian origin. Further studies are needed to elucidate the role of GRIK3 gene in the development of alcohol dependence.

alcoholism; glutamate kainate receptor; GRIK3 gene; polymorphism; rs6691840

nije evidentirano