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Genetic interactions in the adrenergic system genes: analysis of antipsychotic‐induced weight gain
Author(s) -
Luca Vincenzo De,
Souza Renan P.,
Viggiano Emanuela,
Sickert Laertes,
Teo Celine,
Zai Clement,
Tiwari Arun K.,
Müller Daniel J,
Lieberman Jeffery A.,
Volavka Jan,
Meltzer Herbert Y.,
Kennedy James L.
Publication year - 2011
Publication title -
human psychopharmacology: clinical and experimental
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.461
H-Index - 78
eISSN - 1099-1077
pISSN - 0885-6222
DOI - 10.1002/hup.1219
Subject(s) - adrenergic , adrenergic receptor , receptor , biology , weight gain , monoamine oxidase a , antipsychotic , endocrinology , monoamine oxidase , phenotype , medicine , gene , genetics , pharmacology , schizophrenia (object oriented programming) , enzyme , serotonin , body weight , biochemistry , psychiatry
Atypical antipsychotics (AP) have high affinity for many neurotransmitter receptors. Among these receptors, APs are antagonist at α‐adrenergic and β‐adrenergic receptors, and this pharmacological property has been postulated to be involved in the mechanism of action of these drugs with respect to both clinical response and adverse effects. Objective We tested the hypotheses that AP‐induced weight gain is associated with genetic variation in adrenergic receptors and pathway enzymes. We analyzed nine genetic polymorphisms across seven adrenergic genes (ADRA1A, ADRA2A, ADRA2C, ADRB3, DBH, MAOA and COMT). Methods One hundred thirty‐nine patients with schizophrenia were prospectively assessed for AP‐induced weight gain. The HelixTree software (Golden Helix, Bozeman, MT, USA) was employed to detect differences in genotypic distribution between weight gainer and non‐weight gainer groups. Furthermore, for the dopamine β‐hydroxylase haplotype, we were able to obtain both the molecular and the statistical phases, analyzing the phenotype considering both phases. Results Weight gain was not associated with any adrenergic gene. Conclusions Our results suggest that genetic polymorphisms in the adrenergic system may not play a major role in AP‐induced weight gain; however, adrenergic 2A receptor gene that produced previously the most consistent associations with this phenotype showed a significant interaction with the monoamine oxidase A in weight gainers. Copyright © 2011 John Wiley & Sons, Ltd.