Abstract
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.