Funded by the Swiss National Fund for Scientific Research, grant no. 31-120471.
Genetic association of the Phosphoinositide-3 kinase in schizophrenia and bipolar disorder and interaction with a BDNF gene polymorphism
Article first published online: 31 JUL 2012
©2011 The Authors. Brain and Behavior published by Blackwell Publishing Ltd.
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Brain and Behavior
Volume 1, Issue 2, pages 119–124, November 2011
How to Cite
Carrard, A., Salzmann, A., Perroud, N., Gafner, J., Malafosse, A. and Karege, F. (2011), Genetic association of the Phosphoinositide-3 kinase in schizophrenia and bipolar disorder and interaction with a BDNF gene polymorphism. Brain and Behavior, 1: 119–124. doi: 10.1002/brb3.23
- Issue published online: 31 JUL 2012
- Article first published online: 31 JUL 2012
- Received: 24 May 2011; Revised: 08 August 2011; Accepted: 10 September 2011
- BDNF gene;
- bipolar disorder;
- genetic overlaps;
- PIK3C3 gene;
Phosphoinositide-3-kinase, class III (PIK3C3) is a member of the phosphoinosite-3-kinases family, involved in cell signaling, membrane trafficking, and neurodevelopment. Previous studies have indeed shown an association between PIK3C3 gene variants and both bipolar disorder (BD) and schizophrenia (SZ). Brain-derived neurotrophic factor (BDNF) is a neurodevelopmental factor, which can regulate the PI3K signaling pathway. Associations have been reported between BDNF gene polymorphisms and affective and psychotic disorders. The aim of the present study was to replicate an association between PIK3C3 and BDNF gene variants in SZ and BD and a putative epistasis between the two genes. Patients meeting the DSM-IV criteria of BD and SZ were included in this study (98 BD and 79 SZ) as well as 158 healthy controls. Blood DNA was extracted and genotyping was performed either by the polymerase chain reaction (PCR) technique followed by enzymatic digestion or by the high-resolution melt (HRM) method. Genotype and haplotype association was assessed with the UNPHASED statistical program.The results showed one nominal association with BD (P < 0.02) and two risk haplotypes in both SZ (P < 0.001) and BP (P < 0.0005), which survived multiple testing correction. A modest interaction between a BDNF variant and PI3KC3 polymorphism was observed (P < 0.04).These preliminary results confirm the genetic association of PI3K gene variants with both SZ and BD, and support the hypothesis that SZ and BD share a genetic background.