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.


CONCLUSIONS
The data suggest that homozygosity for -1007T could be a rare genetic factor in the development of schizophrenia.
Stopkova
Pavla
P
Department of Psychiatry and Behavioral Sciences, Division of Psychiatry Research, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Vevera
Jan
J
Paclt
Ivo
I
Zukov
Ilja
I
Papolos
Demitri F
DF
Saito
Takuya
T
Lachman
Herbert M
HM
D001483:Base Sequence; D001714:Bipolar Disorder / Q000235:genetics*; D017931:DNA Primers; D024202:Electrophoretic Mobility Shift Assay; D006801:Humans; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011401:Promoter Regions, Genetic; D012559:Schizophrenia / Q000235:genetics*
D017931:DNA Primers; D019869:Phosphatidylinositol 3-Kinases