RATIONALE:

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.

OBJECTIVES:

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.