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


CONCLUSIONS
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.
Martin
Maureen V
MV
Department of Psychiatry and Human Behavior, Univ. of California, Irvine, CA, USA. martinmv@uci.edu
Rollins
Brandi
B
Sequeira
P Adolfo
PA
Mesén
Andrea
A
Byerley
William
W
Stein
Richard
R
Moon
Emily A
EA
Akil
Huda
H
Jones
Edward G
EG
Watson
Stanley J
SJ
Barchas
Jack
J
DeLisi
Lynn E
LE
Myers
Richard M
RM
Schatzberg
Alan
A
Bunney
William E
WE
Vawter
Marquis P
MP
D000328:Adult; D001921:Brain / Q000378:metabolism; D002461:Cell Line, Transformed; D005091:Exons / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D020641:Polymorphism, Single Nucleotide; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012559:Schizophrenia / Q000235:genetics* / Q000473:pathology; D015398:Signal Transduction / Q000235:genetics; D055815:Young Adult
D005947:Glucose