The N251K functional polymorphism in the α2A-adrenoceptor gene is not associated with depression: a study in suicide completers
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α2A-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 α2A-adrenoceptor gene that results in a gain-of-function phenotype. A previous study has suggested an association between completed suicide and this polymorphism.
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).
Postmortem brain DNA was extracted and the α2A-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 α2A-adrenoceptor gene fragment where the polymorphism is located.
The N251K polymorphism was absent in both suicide victim and control groups. No association between the polymorphism and suicide or depression was established.
The N251K polymorphism does not represent a genetic factor to explain the α2A-adrenoceptor hyperactivity in the brains of depressed suicide victims. Association between suicide and this polymorphism was not replicated.
KeywordsAlpha-2 adrenergic receptors Suicide Single nucleotide polymorphism Depression Genetics Human brain Haplotype
This study was supported by grants from the Spanish Ministerio de Sanidad y Consumo [Fondo de Investigación Sanitaria 04/0190 and Redes Temáticas de Investigación Cooperativa Sanitaria (RETICS) G03/179] and Ministerio de Ciencia y Tecnologia (SAF 02/10370E), the Basque Government (ETORTEK and SAIOTEK), the University of the Basque Country (13588/01), and cofinanced by European Regional Development Funds.
The authors wish to thank the staff members of the Basque Institute of Legal Medicine for their cooperation in the study. IM-G and GR are recipients of predoctoral fellowships from RETICS and the Basque Government, respectively.
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