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04:42
Developing a Rat Model for Bipolar Disorder
Published on: May 2, 2025
Functional polymorphisms of HSPA5: possible association with bipolar disorder
Chihiro Kakiuchi1, Mizuho Ishiwata, Shinichiro Nanko
1Laboratory for Molecular Dynamics of Mental Disorders, Brain Science Institute, RIKEN, Wako-shi, Saitama, Japan.
Biochemical and Biophysical Research Communications
|September 20, 2005
Summary
Genetic variations in HSPA5, impacting endoplasmic reticulum stress, may increase bipolar disorder risk. Further research explored these genetic links in Japanese and NIMH trios, and schizophrenia samples.
Area of Science:
- Neuroscience
- Genetics
- Molecular Biology
Background:
- Endoplasmic reticulum (ER) stress response signaling is implicated in bipolar disorder.
- Preliminary studies suggested a genetic association between HSPA5 (GRP78/BiP) and bipolar disorder.
Purpose of the Study:
- To extend the genetic association analysis of HSPA5 in bipolar disorder using larger Japanese case-control and NIMH trio samples.
- To investigate the potential association of HSPA5 with schizophrenia.
- To explore the functional impact of identified HSPA5 polymorphisms on gene expression.
Main Methods:
- Case-control study in Japanese population.
- Analysis of NIMH Genetics Initiative bipolar trio samples.
- Genotyping of HSPA5 polymorphisms.
- Reporter assays to assess promoter activity.
Main Results:
- A nominally significant association of one HSPA5 haplotype was observed in Japanese bipolar disorder samples, but not in schizophrenia.
- No overall association was found in total NIMH trios.
- Exploratory analysis in NIMH trios revealed paternal-specific over-transmission of another HSPA5 haplotype.
- Three common polymorphisms in the HSPA5 promoter were found to alter promoter activity.
Conclusions:
- Promoter polymorphisms in HSPA5 may influence interindividual variability in ER stress response.
- These HSPA5 polymorphisms may represent a genetic risk factor for bipolar disorder.
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