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

Objectives (2C)-adrenoceptors ((2C)-AR) are involved in behavioural responses relevant to psychiatric disorders and suicide completion. The genetic polymorphism (2C)Del322-325-AR confers a loss-of-function phenotype. Functional human studies have associated (2C)Del322-325-AR polymorphism with major depression pathophysiology. The aim of this study was to analyse, for the first time, the association of (2C)Del322-325-AR polymorphism with suicide completion and with related psychiatric disorders: major depression, schizophrenia, opiate and alcohol abuse and dependence. Methods Post-mortem brain DNA was extracted (n=516) and genotyping performed by HaeIII restriction endonuclease digestion of PCR products and DNA fragment analysis on capillary sequencer. Amplified products were sequenced to confirm the presence of the polymorphism. Results The frequency of (2C)Del322-325-AR in suicide (9%, n=236) and non-suicide victims (11%, n=280) was similar. Genotype frequencies for the (2C)Del322-325-AR polymorphism in depressed (15%, n=39) and schizophrenic subjects (18%, n=39) were higher than in controls (7%, n=187), but these differences did not reach statistical significance (P=0.125 and P=0.063, respectively). A selective and significant association of (2C)Del322-325-AR polymorphism with opiate abuse and dependence was found (23%, n=35, P=0.011). Conclusions Our results indicate that (2C)Del322-325-AR may play a role in the pathophysiology of opiate abuse and dependence and raise the interest for larger genetic associative studies.