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

Abstract

Objectives 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. 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 α_2CDel322-325-AR in suicide (9%, n = 236) and non-suicide victims (11%, n = 280) was similar. Genotype frequencies for the α_2CDel322-325-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 α_2CDel322-325-AR polymorphism with opiate abuse and dependence was found (23%, n = 35, P = 0.011). Conclusions 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.

Key words:

• Suicide
• major depressive disorder
• schizophrenia
• opiate abuse and dependence
• α2C-adrenoceptor

Acknowledgements

The authors wish to thank the staff members of the Basque Institute of Legal Medicine, Bilbao for their cooperation in the study.

This work was supported by grants from the Spanish MSC (FIS 04/0190) and MINECO (SAF2004-02784, SAF2009-08460, SAF2013-48586-R), the Basque Government (IT616/13, IT661-13), RTICC (RD12/0036/0060, RD12/0036/0036), RETICS-RTA (RD12/0028/0011) and the European ERDF Fund. G. Rivero was recipient of a predoctoral fellowship from the Basque Government, Spain. These Institutions had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.

Disclosure statement

None to declare.