Protein kinase cAMP-dependent regulatory type II beta (PRKAR2B) gene variants in antipsychotic-induced weight gain

Gagliano, Sarah A. and Tiwari, Arun K. and Freeman, Natalie and Lieberman, Jeffrey A. and Meltzer, Herbert Y. and Kennedy, James L. and Knight, Jo and Müller, Daniel J. (2014) Protein kinase cAMP-dependent regulatory type II beta (PRKAR2B) gene variants in antipsychotic-induced weight gain. Human Psychopharmacology: Clinical and Experimental, 29 (4). pp. 330-335. ISSN 0885-6222

Abstract

OBJECTIVE: Antipsychotics are effective in treating schizophrenia symptoms. However, the use of clozapine and olanzapine in particular are associated with significant weight gain. Mouse and human studies suggest that the protein kinase cAMP-dependent regulatory type II beta (PRKAR2B) gene may be involved in energy metabolism, and there is evidence that it is associated with clozapine's effects on triglyceride levels. We aimed at assessing PRKAR2B's role in antipsychotic-induced weight gain in schizophrenia patients. METHODS: DNA samples from adult schizophrenia or schizoaffective disorder patients of mixed ancestry were genotyped, and weight gain was assessed. We analyzed 16 tag single-nucleotide polymorphisms across the PRKAR2B gene in a Caucasian subset treated either with clozapine or olanzapine (N = 99). Linear regression based on an additive model was performed with the inclusion of relevant covariates. RESULTS: Normalized per cent weight change was analyzed, revealing that patients with the minor allele at rs9656135 had a mean weight increase of 4.1%, whereas patients without this allele had an increase of 3.4%. This association is not significant after correcting for multiple testing. CONCLUSIONS: Because of limited power, PRKAR2B's role in antipsychotic-induced weight gain is unclear, but biological evidence suggests that PRKAR2B may be involved. Further research in larger sample sizes is warranted.