Human MIP synthase splice variants in bipolar disorder

Objectives: Alternative splicing allows the production of multiple gene products with different functions from a given sequence, affecting cellular function control. Tissue-specific splicing is most prevalent in the brain. We therefore investigate whether splice variants contribute to complex psychiatric disorders. A database search suggested that the myo-inositol-1-phosphate (MIP) synthase gene, possibly involved in pathophysiology of bipolar disorder, has splice variants. Methods: Human RNA was purified from lymphocytes and postmortem brain. MIP synthase alternative splice variants were amplified using reverse transcription-polymerase chain reaction. Results: The bioinformatics finding was confirmed in both tissues. No difference in lymphocyte MIP synthase mRNA splice-variant levels was found between bipolar patients and controls. However, patients with family history of a major psychiatric disorder had significantly higher levels of the variant lacking exons 3 and 4 versus patients with no family history and controls. Conclusions: As alternative splicing may be a mechanism by which the ∼30,000 genes are amplified in mammalian brain, further studies with other candidate genes for psychiatric disorders are needed.