Altered gene expression profiles in the frontal cortex of cirrhotic alcoholics.
BACKGROUND
Cirrhosis is the result of chronic liver disease that causes scarring and dysfunction of the liver. The disease is a common concomitant condition resulting from sustained exposure to alcohol. Heavy alcohol use results in brain damage that is generally more severe in cirrhotic compared with noncirrhotic alcoholics. We examined, at the cellular level, gene expression in the frontal cortex of cirrhotic alcoholics.


METHODS
Gene expression profiles were compared between cirrhotic and noncirrhotic alcoholics using approximately 47,000 element cDNA microarrays.


RESULTS
Widespread differences in transcriptome patterns were observed in cirrhotic compared with noncirrhotic alcoholics and these differences in gene expression accurately distinguished cirrhotic from noncirrhotic alcoholics. Functionally related groups of genes were identified that are involved in cell adhesion, mitochondrial function, synaptic transmission, apoptosis, and cell proliferation. Both astrocytes and neuronal cells were affected at the transcriptional level. The regulated genes are involved in neurite growth, neuronal cell adhesion, synaptic vesicle release, and postsynaptic neurotransmission.


CONCLUSIONS
These changes in the transcriptome likely contribute to the more severe brain dysfunction in cirrhotic alcoholics.
Liu
Jianwen
J
Waggoner Center for Alcohol and Addiction Research, University of Texas at Austin, Austin, Texas 78712, USA.
Lewohl
Joanne M
JM
Harris
R Adron
RA
Dodd
Peter R
PR
Mayfield
R Dayne
RD
D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D016022:Case-Control Studies; D002448:Cell Adhesion / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism* / Q000473:pathology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D008104:Liver Cirrhosis, Alcoholic / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000235:genetics / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D009435:Synaptic Transmission / Q000235:genetics / Q000502:physiology