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.
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)-adrenoceptorhyperactivity in the brains of depressed suicide victims. Association between suicide and this polymorphism was not replicated.
Authors: A M González; J Pascual; J J Meana; F Barturen; C del Arco; A Pazos; J A García-Sevilla Journal: J Neurochem Date: 1994-07 Impact factor: 5.372