A polymorphism in the PDLIM5 gene associated with gene expression and schizophrenia.
- Authors
- Horiuchi, Yasue; Arai, Makoto; Niizato, Kazuhiro; Iritani, Shyuji; Noguchi, Emiko; Ohtsuki, Tsuyuka; Koga, Minori; Kato, Tadafumi; Itokawa, Masanari; Arinami, Tadao
- Year
- 2006
- Journal
- Biological psychiatry
- PMID
- 16213469
- DOI
- 10.1016/j.biopsych.2005.07.041
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.
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