Alpha2C-adrenoceptor Del322-325 polymorphism and risk of psychiatric disorders: significant association with opiate abuse and dependence

Abstract

<p><b>Objectives</b> α_2C-adrenoceptors (α_2C-AR) are involved in behavioural responses relevant to psychiatric disorders and suicide completion. The genetic polymorphism α_2CDel322-325-AR confers a loss-of-function phenotype. Functional human studies have associated α_2CDel322-325-AR polymorphism with major depression pathophysiology. The aim of this study was to analyse, for the first time, the association of α_2CDel322-325-AR polymorphism with suicide completion and with related psychiatric disorders: major depression, schizophrenia, opiate and alcohol abuse and dependence. <b>Methods</b> Post-mortem brain DNA was extracted (<i>n</i> = 516) and genotyping performed by <i>Hae</i>III restriction endonuclease digestion of PCR products and DNA fragment analysis on capillary sequencer. Amplified products were sequenced to confirm the presence of the polymorphism. <b>Results</b> The frequency of α_2CDel322-325-AR in suicide (9%, <i>n</i> = 236) and non-suicide victims (11%, <i>n</i> = 280) was similar. Genotype frequencies for the α_2CDel322-325-AR polymorphism in depressed (15%, <i>n</i> = 39) and schizophrenic subjects (18%, <i>n</i> = 39) were higher than in controls (7%, <i>n</i> = 187), but these differences did not reach statistical significance (<i>P</i> = 0.125 and <i>P</i> = 0.063, respectively). A selective and significant association of α_2CDel322-325-AR polymorphism with opiate abuse and dependence was found (23%, <i>n</i> = 35, <i>P</i> = 0.011). <b>Conclusions</b> Our results indicate that α_2CDel322-325-AR may play a role in the pathophysiology of opiate abuse and dependence and raise the interest for larger genetic associative studies.</p