Naslov
The association of GABA-A receptor alpha2 subunit gene (GABRA2) with alcohol-related suicidal behaviour

Autori
Svob Strac, Dubravka ; Nedic Erjavec, Gordana ; Nikolac Perkovic, Matea ; Nenadic Sviglin, Korona ; Muck-Seler, Dorotea ; Pivac, Nela

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Book of Abstracts 4. Croatian Congress of Neuroscience / / - Zagreb : Hrvatsko društvo za neuroznanost ; Hrvatski institut za istraživanje mozga Medicinskog fakulteta Sveučilišta u Zagrebu, 2013, 30-30

Skup
4th Croatian Congress of Neuroscience

Mjesto i datum
Zagreb, Hrvatska, 20.09.2013. - 21.09.2013

Vrsta sudjelovanja
Poster

Vrsta recenzije
Domaća recenzija

Ključne riječi
GABA-A receptor; GABRA2 gene; alcoholism; suicidal behaviour; polymorphism

Sažetak
Alcohol dependence has been associated with an increased risk for suicidal behavior and growing evidence indicated that genetic factors contribute to suicide risk. GABA-A receptors, the major fast inhibitory neurotransmitter receptors in the brain, have been implicated in both acute and chronic effects of alcohol, including tolerance, dependence and withdrawal. Moreover, some studies suggested that dysfunction in GABAergic neurotransmitter system also plays a role in the neurobiology of suicidal behaviour. As recent studies demonstrated that multiple markers in the gene encoding the GABA-A receptor alpha2 subunit (GABRA2) are associated with alcoholism in different populations of European ancestry, the aim of our study was to examine the allelic and haplotypic association of GABRA2 gene with alcohol-related suicidal behaviour in subjects of Croatian origin. Hence, we genotyped 3 single nucleotide polymorphisms across the GABRA2 gene located on the chromosome 4p in samples of 355 alcoholic patients (280 males and 75 females), subdivided according to the presence of suicide attempt during life-time. Alcohol dependence was diagnosed based on the DSM-IV criteria, while suicide attempt was assessed by the suicide relevant questions from the Hamilton Rating Scale for Depression and a structured psychiatric interview. Genotyping of GABRA2 polymorphisms (rs567926, rs279858 and rs9291283) was performed using TaqMan Real-Time allelic discrimination after extraction of DNA from the whole blood with a salting out procedure. The results demonstrated an association of SNP rs279858 with an increased risk of suicide attempt in alcoholic patients (χ2 = 6.551, p = 0.038). Namely, subjects with alcohol dependence who attempted suicide had higher frequency of T allele (χ2 = 5.571, p = 0.018), as well as homozygous TT genotype versus C carriers (χ2 = 6.256, p = 0.012). Moreover, haplotype analysis revealed that G-T-G alcoholic haplotype carriers were more likely to report suicide attempt (χ2 = 4.053, p = 0.044). To our knowledge these are the first findings suggesting the involvement of GABRA2 gene in the alcoholism- related suicidal behaviour. However, further studies are needed to investigate whether these GABRA2 gene variants are associated with an increased risk of suicidal attempt(s) in general population, or these associations exist only in alcoholic patients.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA