Alpha 2A adrenergic receptor gene and suicide

Sequeira, Adolfo; Mamdani, Firoza; Lalovic, Aleksandra; Anguelova, Milena; Lesage, Alain; Seguin, Monique; Chawky, Nadia; Desautels, Alex; Turecki, Gustavo

doi:10.1016/j.psychres.2003.12.002

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Volume 125, Issue 2 , Pages 87-93, 15 February 2004

Alpha 2A adrenergic receptor gene and suicide

Adolfo Sequeira
- McGill Group for Suicide Studies, Douglas Hospital, McGill University, 6875 LaSalle Blvd., Verdun, QC, Canada H4H 1R3
Firoza Mamdani
- McGill Group for Suicide Studies, Douglas Hospital, McGill University, 6875 LaSalle Blvd., Verdun, QC, Canada H4H 1R3
Aleksandra Lalovic
- McGill Group for Suicide Studies, Douglas Hospital, McGill University, 6875 LaSalle Blvd., Verdun, QC, Canada H4H 1R3
Milena Anguelova
- McGill Group for Suicide Studies, Douglas Hospital, McGill University, 6875 LaSalle Blvd., Verdun, QC, Canada H4H 1R3
Alain Lesage
- Fernand Seguin Research Center, Université de Montréal, Montreal, Canada
Monique Seguin
- McGill Group for Suicide Studies, Douglas Hospital, McGill University, 6875 LaSalle Blvd., Verdun, QC, Canada H4H 1R3
Nadia Chawky
- McGill Group for Suicide Studies, Douglas Hospital, McGill University, 6875 LaSalle Blvd., Verdun, QC, Canada H4H 1R3
Alex Desautels
- McGill Group for Suicide Studies, Douglas Hospital, McGill University, 6875 LaSalle Blvd., Verdun, QC, Canada H4H 1R3
Gustavo Turecki
- McGill Group for Suicide Studies, Douglas Hospital, McGill University, 6875 LaSalle Blvd., Verdun, QC, Canada H4H 1R3
- Corresponding author. Tel.: +1-514-7616131x2369; fax: +1-514-7623011

Received 14 February 2003; received in revised form 5 December 2003; accepted 15 December 2003.

Abstract

Suicide is a complex trait resulting from the interaction of several predisposing factors, among which genes seem to play an important role. Alterations in the noradrenergic system have been observed in postmortem brain studies of suicide victims when compared to controls. The purpose of this study was to test the hypothesis that genetic variants of the α_2A adrenergic receptor gene are implicated in suicide and/or have a modulatory effect on personality traits that are believed to mediate suicidal behavior. We studied a sample of suicides (N=110) and control subjects (N=130) for genetic variation at four loci, including three in the promoter region (g-1800t, c-1291 g and the g-261a) of the α_2A adrenergic receptor gene, and a potentially functional locus, N251K, which leads to an amino acid change (asparagine to lysine). No significant differences were observed at the promoter loci in terms of allelic or genotypic distribution between suicides and controls. However, analysis of the functional polymorphism N251K revealed that the 251 K allele was only present among suicides, though only three suicide cases had this allele, two of which were homozygous. These results are preliminary. If confirmed, they suggest that variation at the α_2A adrenergic receptor gene may play a role in a small proportion of suicide cases.

Keywords: Genetic variation, Personality measurements, Adrenoceptor, Functional polymorphism, Genotypes, Noradrenergic system, Impulsive behavior