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Open Access Highly Accessed Research article

Exon expression in lymphoblastoid cell lines from subjects with schizophrenia before and after glucose deprivation

Maureen V Martin1, Brandi Rollins1, P Adolfo Sequeira1, Andrea Mesén23, William Byerley4, Richard Stein1, Emily A Moon1, Huda Akil5, Edward G Jones6, Stanley J Watson5, Jack Barchas7, Lynn E DeLisi8, Richard M Myers9, Alan Schatzberg10, William E Bunney1 and Marquis P Vawter1*

Author Affiliations

1 Department of Psychiatry and Human Behavior, Univ. of California, Irvine, CA, USA

2 Psychiatric Genetics Research Center, Heredia, Costa Rica

3 Hospital Nacional Psiquiatrico, Pavas, San Jose, Costa Rica

4 Psychiatry, Univ. of California, San Francisco, CA, USA

5 Molecular & Behavioral Neuroscience Institute, Univ. of Michigan, MI, USA

6 Neuroscience Center, Univ. of California Davis, CA, USA

7 Psychiatry, Cornell Univ., New York NY, USA

8 Psychiatry, New York Univ., New York NY, USA

9 Hudson Alpha, Huntsville AB, USA

10 Psychiatry, Stanford University Palo Alto, CA, USA

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BMC Medical Genomics 2009, 2:62  doi:10.1186/1755-8794-2-62

Published: 22 September 2009

Abstract

Background

The purpose of this study was to examine the effects of glucose reduction stress on lymphoblastic cell line (LCL) gene expression in subjects with schizophrenia compared to non-psychotic relatives.

Methods

LCLs were grown under two glucose conditions to measure the effects of glucose reduction stress on exon expression in subjects with schizophrenia compared to unaffected family member controls. A second aim of this project was to identify cis-regulated transcripts associated with diagnosis.

Results

There were a total of 122 transcripts with significant diagnosis by probeset interaction effects and 328 transcripts with glucose deprivation by probeset interaction probeset effects after corrections for multiple comparisons. There were 8 transcripts with expression significantly affected by the interaction between diagnosis and glucose deprivation and probeset after correction for multiple comparisons. The overall validation rate by qPCR of 13 diagnosis effect genes identified through microarray was 62%, and all genes tested by qPCR showed concordant up- or down-regulation by qPCR and microarray. We assessed brain gene expression of five genes found to be altered by diagnosis and glucose deprivation in LCLs and found a significant decrease in expression of one gene, glutaminase, in the dorsolateral prefrontal cortex (DLPFC). One SNP with previously identified regulation by a 3' UTR SNP was found to influence IRF5 expression in both brain and lymphocytes. The relationship between the 3' UTR rs10954213 genotype and IRF5 expression was significant in LCLs (p = 0.0001), DLPFC (p = 0.007), and anterior cingulate cortex (p = 0.002).

Conclusion

Experimental manipulation of cells lines from subjects with schizophrenia may be a useful approach to explore stress related gene expression alterations in schizophrenia and to identify SNP variants associated with gene expression.