The N251K functional polymorphism in the alpha(2A)-adrenoceptor gene is not associated with depression: a study in suicide completers.
BACKGROUND
alpha(2A)-Adrenoceptor up-regulation and supersensitivity have been described in the postmortem brains of depressed suicide victims and in the platelets of depressed subjects. The C to G transversion at nucleotide 753 (Asn to Lys change at amino acid 251 or N251K) is a low-frequency polymorphism of the alpha(2A)-adrenoceptor gene that results in a gain-of-function phenotype. A previous study has suggested an association between completed suicide and this polymorphism.


OBJECTIVE
The single functional polymorphism N251K was tested in a large sample (n=214) of completed suicides, controlling for the antemortem psychiatric diagnosis, and matched controls (n=176).


METHODS
Postmortem brain DNA was extracted and the alpha(2A)-adrenoceptor gene fragment was amplified by polymerase chain reaction, followed by a StyI restriction endonuclease digestion. Amplified products were sequenced to confirm the presence of the alpha(2A)-adrenoceptor gene fragment where the polymorphism is located.


RESULTS
The N251K polymorphism was absent in both suicide victim and control groups. No association between the polymorphism and suicide or depression was established.


CONCLUSIONS
The N251K polymorphism does not represent a genetic factor to explain the alpha(2A)-adrenoceptor hyperactivity in the brains of depressed suicide victims. Association between suicide and this polymorphism was not replicated.
Martín-Guerrero
Idoia
I
Department of Genetics, Physical Anthropology and Animal Physiology, University of the Basque Country, Leioa, Bizkaia, Spain.
Callado
Luis F
LF
Saitua
Koldo
K
Rivero
Guadalupe
G
García-Orad
Africa
A
Meana
J Javier
JJ
D001921:Brain / Q000378:metabolism; D003865:Major Depressive Disorder / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics*; D013405:Suicide
C547768:ADRA2A protein, human; D018341:Receptors, Adrenergic, alpha-2