title: Genes and gene expression in the brains of human alcoholics.
abstract: Chronic alcohol misuse by human subjects leads to neuronal loss in regions such as the superior frontal cortex (SFC). Propensity to alcoholism is associated with several genes. gamma-Aminobutyric acid (GABA)(A) receptor expression differs between alcoholics and controls, whereas glutamate receptor differences are muted. We determined whether genotype differentiated the regional presentation of GABA(A) and glutamate-NMDA (N-methyl-d-aspartate) receptors in SFC. Autopsy tissue was obtained from alcoholics without comorbid disease, alcoholics with liver cirrhosis, and matched controls. ADH1C, DRD2B, EAAT2, and APOE genotypes modulated GABA(A)-beta subunit protein expression in SFC toward a less-effective form of the receptor. Most genotypes did not divide alcoholics and controls on glutamate-NMDA receptor pharmacology, although gender and cirrhosis did. Genotype may affect amino acid transmission locally to influence neuronal vulnerability.
authors.affiliation: School of Molecular and Microbial Science, University of Queensland, Brisbane 4072, Australia. p.dodd@uq.edu.au
authors.forename: Peter R
authors.initials: PR
authors.lastname: Dodd
authors.forename: S Tracey
authors.initials: ST
authors.lastname: Buckley
authors.forename: Allison L
authors.initials: AL
authors.lastname: Eckert
authors.forename: Philomena F
authors.initials: PF
authors.lastname: Foley
authors.forename: David J
authors.initials: DJ
authors.lastname: Innes
mesh_terms: D000437:Alcoholism / Q000235:genetics* / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D015870:Gene Expression; D006801:Humans; D008104:Liver Cirrhosis, Alcoholic / Q000235:genetics* / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011963:Receptors, GABA-A / Q000235:genetics* / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*
chemical_list: D018691:Excitatory Amino Acid Antagonists; D020033:Protein Isoforms; D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate