Genetic interactions in the adrenergic system genes: analysis of antipsychotic-induced weight gain
Article first published online: 8 AUG 2011
Copyright © 2011 John Wiley & Sons, Ltd.
Human Psychopharmacology: Clinical and Experimental
Volume 26, Issue 6, pages 386–391, August 2011
How to Cite
Luca, V. D., Souza, R. P., Viggiano, E., Sickert, L., Teo, C., Zai, C., Tiwari, A. K., Müller, D. J., Lieberman, J. A., Volavka, J., Meltzer, H. Y. and Kennedy, J. L. (2011), Genetic interactions in the adrenergic system genes: analysis of antipsychotic-induced weight gain. Hum. Psychopharmacol. Clin. Exp., 26: 386–391. doi: 10.1002/hup.1219
- Issue published online: 26 AUG 2011
- Article first published online: 8 AUG 2011
- Manuscript Accepted: 11 JUN 2011
- Manuscript Revised: 30 MAY 2011
- Manuscript Received: 5 FEB 2011
- genetic polymorphisms;
- metabolic syndrome
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.
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).
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.
Weight gain was not associated with any adrenergic gene.
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.