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 Mesén^2,3 , 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

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

²Psychiatric Genetics Research Center, Heredia, Costa Rica

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

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

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

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

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

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

⁹Hudson Alpha, Huntsville AB, USA

¹⁰Psychiatry, Stanford University Palo Alto, CA, USA

author email corresponding author email

BMC Medical Genomics 2009, 2:62doi: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.