Screening of PIP5K2A promoter region for mutations in bipolar disorder and schizophrenia

OBJECTIVE: To analyze the promoter region of PIP5K2A, a phosphatidylinositol 4-phosphate 5-kinase that maps to 10p in a region linked to both bipolar disorder and schizophrenia. METHODS: The promoter region was screened by single-strand conformation polymorphism analysis and DNA sequencing. Allele frequencies were determined in a case-control study. Functional significance of a promoter variant was determined by electromobility gel shift assays. RESULTS: Homozygosity for a rare putative promoter variant, -1007C-->T, was found in only two patients with schizophrenia and in no controls or bipolar patients. The variant forms a 7/8 base match for the binding site of Oct-1, a member of the POU homeodomain family. Electromobility gel shift assays revealed increased binding of a brain-specific nuclear protein to the -1007T allele compared with -1007C. CONCLUSION: The data suggest that homozygosity for -1007T could be a rare genetic factor in the development of schizophrenia.