A polymorphism in the PDLIM5 gene associated with gene expression and schizophrenia.
BACKGROUND
Results of recent DNA microarray analyses of postmortem brains of patients with schizophrenia revealed that expression of the PDZ and LIM domain 5 gene (PDLIM5) is increased. In the present study, we examined whether polymorphisms in PDLIM5 are associated with schizophrenia.


METHODS
We screened for mutations in PDLIM5 in 24 Japanese patients with schizophrenia and evaluated the associations of the identified polymorphisms with schizophrenia in a Japanese case-control population (total samples, 278 schizophrenia patients and 462 control subjects). Expression of PDLIM5 was quantified by real-time quantitative polymerase chain reaction (PCR) in postmortem prefrontal cortex of 34 schizophrenia patients. Electrophoretic mobility shift assay (EMSA) was performed to examine whether a polymorphism influences nuclear protein binding.


RESULTS
We identified 27 polymorphisms in PDLIM5 and found associations between polymorphisms (rs2433320 and rs2433322) in the 5' region of the gene and schizophrenia (p = .004). Real-time quantitative PCR revealed that these polymorphisms influenced gene expression (p = .007). An EMSA showed that the different alleles of the rs2433320 polymorphism bound differently to nuclear proteins.


CONCLUSIONS
These results suggest that PDLIM5 might play a role in genetic susceptibility to schizophrenia.
Horiuchi
Yasue
Y
Department of Medical Genetics, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
Arai
Makoto
M
Niizato
Kazuhiro
K
Iritani
Shyuji
S
Noguchi
Emiko
E
Ohtsuki
Tsuyuka
T
Koga
Minori
M
Kato
Tadafumi
T
Itokawa
Masanari
M
Arinami
Tadao
T
D000328:Adult; D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D000076122:Disks Large Homolog 4 Protein; D005260:Female; D015870:Gene Expression / Q000502:physiology*; D005787:Gene Frequency / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D060850:LIM-Homeodomain Proteins; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017397:Prefrontal Cortex / Q000473:pathology; D012559:Schizophrenia / Q000235:genetics*; D014157:Transcription Factors
C501444:DLG4 protein, human; D000076122:Disks Large Homolog 4 Protein; D005819:Genetic Markers; D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins; C491186:LHX5 protein, human; D060850:LIM-Homeodomain Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D014157:Transcription Factors