title: Alpha2C-adrenoceptor Del322-325 polymorphism and risk of psychiatric disorders: significant association with opiate abuse and dependence.
abstract: Objectives α2C-adrenoceptors (α2C-AR) are involved in behavioural responses relevant to psychiatric disorders and suicide completion. The genetic polymorphism α2CDel322-325-AR confers a loss-of-function phenotype. Functional human studies have associated α2CDel322-325-AR polymorphism with major depression pathophysiology. The aim of this study was to analyse, for the first time, the association of α2CDel322-325-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 α2CDel322-325-AR in suicide (9%, n = 236) and non-suicide victims (11%, n = 280) was similar. Genotype frequencies for the α2CDel322-325-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 α2CDel322-325-AR polymorphism with opiate abuse and dependence was found (23%, n = 35, P = 0.011). Conclusions Our results indicate that α2CDel322-325-AR may play a role in the pathophysiology of opiate abuse and dependence and raise the interest for larger genetic associative studies.
authors.affiliation: a Department of Pharmacology , University of the Basque Country (UPV/EHU) and Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM) , Spain ;|c BioCruces Health Research Institute , Spain ;
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Rivero
authors.affiliation: b Department of Genetics, Physical Anthropology and Animal Physiology , University of the Basque Country (UPV/EHU) , Spain ;|c BioCruces Health Research Institute , Spain ;
authors.forename: Idoia
authors.initials: I
authors.lastname: Martín-Guerrero
authors.affiliation: b Department of Genetics, Physical Anthropology and Animal Physiology , University of the Basque Country (UPV/EHU) , Spain ;|c BioCruces Health Research Institute , Spain ;
authors.forename: Elena
authors.initials: E
authors.lastname: de Prado
authors.affiliation: a Department of Pharmacology , University of the Basque Country (UPV/EHU) and Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM) , Spain ;|c BioCruces Health Research Institute , Spain ;
authors.forename: Ane M
authors.initials: AM
authors.lastname: Gabilondo
authors.affiliation: a Department of Pharmacology , University of the Basque Country (UPV/EHU) and Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM) , Spain ;|c BioCruces Health Research Institute , Spain ;
authors.forename: Luis F
authors.initials: LF
authors.lastname: Callado
authors.affiliation: d Laboratory of Neuropharmacology , IUNICS-IdISPa, University of the Balearic Islands (UIB), and Redes Temáticas de Investigación Cooperativa en Salud-Red de Trastornos Adictivos (RETICS-RTA) , Spain.
authors.forename: Jesús A
authors.initials: JA
authors.lastname: García-Sevilla
authors.affiliation: b Department of Genetics, Physical Anthropology and Animal Physiology , University of the Basque Country (UPV/EHU) , Spain ;|c BioCruces Health Research Institute , Spain ;
authors.forename: África
authors.initials: Á
authors.lastname: García-Orad
authors.affiliation: a Department of Pharmacology , University of the Basque Country (UPV/EHU) and Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM) , Spain ;|c BioCruces Health Research Institute , Spain ;
authors.forename: J Javier
authors.initials: JJ
authors.lastname: Meana
mesh_terms: D000328:Adult; D000437:Alcoholism / Q000235:genetics*; D001344:Autopsy; D003865:Major Depressive Disorder / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009293:Opioid-Related Disorders / Q000235:genetics*; D011110:Polymorphism, Genetic; D017397:Prefrontal Cortex / Q000473:pathology; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics*; D012189:Retrospective Studies; D012559:Schizophrenia / Q000235:genetics*; D013405:Suicide / Q000706:statistics & numerical data*
chemical_list: C547774:ADRA2C protein, human; D018341:Receptors, Adrenergic, alpha-2
keywords: Suicide; major depressive disorder; opiate abuse and dependence; schizophrenia; α2C-adrenoceptor