Genes and gene expression in the brains of human alcoholics.
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.
Dodd
Peter R
PR
School of Molecular and Microbial Science, University of Queensland, Brisbane 4072, Australia. p.dodd@uq.edu.au
Buckley
S Tracey
ST
Eckert
Allison L
AL
Foley
Philomena F
PF
Innes
David J
DJ
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*
D018691:Excitatory Amino Acid Antagonists; D020033:Protein Isoforms; D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate