title: Exon microarray analysis of human dorsolateral prefrontal cortex in alcoholism.
abstract: BACKGROUND
  Alcohol abuse is associated with cellular and biochemical disturbances that impact upon protein and nucleic acid synthesis, brain development, function, and behavioral responses. To further characterize the genetic influences in alcoholism and the effects of alcohol consumption on gene expression, we used a highly sensitive exon microarray to examine mRNA expression in human frontal cortex of alcoholics and control males.
  
  
  METHODS
  Messenger RNA was isolated from the dorsolateral prefrontal cortex (dlPFC; Brodmann area 9) of 7 adult alcoholic (6 males, 1 female, mean age 49 years) and 7 matched controls. Affymetrix Human Exon 1.0 ST array was performed according to standard procedures and the results analyzed at the gene level. Microarray findings were validated using quantitative reverse transcription polymerase chain reaction, and the ontology of disturbed genes characterized using Ingenuity Pathway Analysis (IPA).
  
  
  RESULTS
  Decreased mRNA expression was observed for genes involved in cellular adhesion (e.g., CTNNA3, ITGA2), transport (e.g., TF, ABCA8), nervous system development (e.g., LRP2, UGT8, GLDN), and signaling (e.g., RASGRP3, LGR5) with influence over lipid and myelin synthesis (e.g., ASPA, ENPP2, KLK6). IPA identified disturbances in network functions associated with neurological disease and development including cellular assembly and organization impacting on psychological disorders.
  
  
  CONCLUSIONS
  Our data in alcoholism support a reduction in expression of dlPFC mRNA for genes involved with neuronal growth, differentiation, and signaling that targets white matter of the brain.
authors.affiliation: Department of Psychiatry and Behavioral Sciences , University of Kansas School of Medicine, Kansas City, Kansas.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Manzardo
authors.forename: Sumedha
authors.initials: S
authors.lastname: Gunewardena
authors.forename: Kun
authors.initials: K
authors.lastname: Wang
authors.forename: Merlin G
authors.initials: MG
authors.lastname: Butler
mesh_terms: D000328:Adult; D000437:Alcoholism / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D005091:Exons / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D017397:Prefrontal Cortex / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
keywords: Affymetrix; Alcoholism; Exon Microarray; Frontal Cortex; Myelin