A polymorphism in the PDLIM5 gene associated with gene expression and schizophrenia.

Abstract

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.

• Authors: Yasue Horiuchi, Makoto Arai, Kazuhiro Niizato, Shyuji Iritani, Emiko Noguchi, Tsuyuka Ohtsuki, Minori Koga, Tadafumi Kato, Masanari Itokawa, Tadao Arinami
• Journal: Biological psychiatry (Biol Psychiatry) Vol. 59 Issue 5 Pg. 434-9 (Mar 01 2006) ISSN: 0006-3223 [Print] United States
• PMID: 16213469 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DLG4 protein, human
• Disks Large Homolog 4 Protein
• Genetic Markers
• Homeodomain Proteins
• Intracellular Signaling Peptides and Proteins
• LHX5 protein, human
• LIM-Homeodomain Proteins
• Membrane Proteins
• Nerve Tissue Proteins
• Transcription Factors

Topics

• Adult
• Aged
• Alleles
• Case-Control Studies
• DNA Mutational Analysis
• Disks Large Homolog 4 Protein
• Female
• Gene Expression (physiology)
• Gene Frequency (genetics)
• Genetic Markers (genetics)
• Homeodomain Proteins (genetics)
• Humans
• Intracellular Signaling Peptides and Proteins (genetics)
• LIM-Homeodomain Proteins
• Male
• Membrane Proteins (genetics)
• Middle Aged
• Nerve Tissue Proteins (genetics)
• Polymerase Chain Reaction
• Polymorphism, Genetic (genetics)
• Polymorphism, Single Nucleotide (genetics)
• Prefrontal Cortex (pathology)
• Schizophrenia (genetics)
• Transcription Factors