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

Area of Science:

• Neurogenetics
• Molecular Psychiatry

Background:

• Elevated PDZ and LIM domain 5 gene (PDLIM5) expression observed in postmortem brains of schizophrenia patients.
• Previous studies indicated increased PDLIM5 expression in schizophrenia.

Purpose of the Study:

• To investigate the association between PDLIM5 gene polymorphisms and schizophrenia.
• To determine if identified PDLIM5 polymorphisms influence gene expression and nuclear protein binding.

Main Methods:

• Screening for PDLIM5 mutations in Japanese schizophrenia patients.
• Case-control association study in a Japanese population (278 patients, 462 controls).
• Real-time quantitative PCR for PDLIM5 expression analysis and Electrophoretic mobility shift assay (EMSA) for protein binding.

Main Results:

• Twenty-seven PDLIM5 polymorphisms identified; two (rs2433320, rs2433322) in the 5' region associated with schizophrenia (p = .004).
• These polymorphisms significantly influenced PDLIM5 gene expression (p = .007).
• EMSA demonstrated differential nuclear protein binding for the rs2433320 polymorphism alleles.

Conclusions:

• PDLIM5 gene polymorphisms are associated with schizophrenia.
• The findings suggest PDLIM5 plays a role in the genetic susceptibility to schizophrenia.