Gene Expression in Human Alcoholism: Microarray Analysis of Frontal Cortex

Authors

  • Joanne M. Lewohl,

    1. Waggoner Center for Alcohol and Addiction Research (JML, RAH), University of Texas at Austin, Austin, Texas; Department of Biochemistry (JML, PRD), University of Queensland, St Lucia, Australia; and Ernest Gallo Clinic and Research Center (LW, MFM, LZ), University of California at San Francisco, San Francisco California.
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  • Long Wang,

    1. Waggoner Center for Alcohol and Addiction Research (JML, RAH), University of Texas at Austin, Austin, Texas; Department of Biochemistry (JML, PRD), University of Queensland, St Lucia, Australia; and Ernest Gallo Clinic and Research Center (LW, MFM, LZ), University of California at San Francisco, San Francisco California.
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  • Michael F. Miles,

    1. Waggoner Center for Alcohol and Addiction Research (JML, RAH), University of Texas at Austin, Austin, Texas; Department of Biochemistry (JML, PRD), University of Queensland, St Lucia, Australia; and Ernest Gallo Clinic and Research Center (LW, MFM, LZ), University of California at San Francisco, San Francisco California.
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  • Li Zhang,

    1. Waggoner Center for Alcohol and Addiction Research (JML, RAH), University of Texas at Austin, Austin, Texas; Department of Biochemistry (JML, PRD), University of Queensland, St Lucia, Australia; and Ernest Gallo Clinic and Research Center (LW, MFM, LZ), University of California at San Francisco, San Francisco California.
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  • Peter R. Dodd,

    1. Waggoner Center for Alcohol and Addiction Research (JML, RAH), University of Texas at Austin, Austin, Texas; Department of Biochemistry (JML, PRD), University of Queensland, St Lucia, Australia; and Ernest Gallo Clinic and Research Center (LW, MFM, LZ), University of California at San Francisco, San Francisco California.
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  • R. Adron Harris

    Corresponding author
    1. Waggoner Center for Alcohol and Addiction Research (JML, RAH), University of Texas at Austin, Austin, Texas; Department of Biochemistry (JML, PRD), University of Queensland, St Lucia, Australia; and Ernest Gallo Clinic and Research Center (LW, MFM, LZ), University of California at San Francisco, San Francisco California.
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  • Supported by funds from the Texas Commission on Alcoholism and Drug Abuse, NIH Grant AA06399, the National Health and Medical Research Council (NH&MRC) of Australia (Grant 981723), and funds provided by the State of California through University of California at San Francisco for research on alcoholism and drug abuse.

Dr. R. A. Harris, Molecular Biology Building 1.124, University of Texas A4800, Austin, TX 78712; Fax: 512-232-2525; E-mail: harris@mail.utexas.edu

Abstract

Background: Changes in brain gene expression are thought to be responsible for the tolerance, dependence, and neurotoxicity produced by chronic alcohol abuse, but there has been no large scale study of gene expression in human alcoholism.

Methods: RNA was extracted from postmortem samples of superior frontal cortex of alcoholics and nonalcoholics. Relative levels of RNA were determined by array techniques. We used both cDNA and oligonucleotide microarrays to provide coverage of a large number of genes and to allow cross-validation for those genes represented on both types of arrays.

Results: Expression levels were determined for over 4000 genes and 163 of these were found to differ by 40% or more between alcoholics and nonalcoholics. Analysis of these changes revealed a selective reprogramming of gene expression in this brain region, particularly for myelin-related genes which were down-regulated in the alcoholic samples. In addition, cell cycle genes and several neuronal genes were changed in expression.

Conclusions: These gene expression changes suggest a mechanism for the loss of cerebral white matter in alcoholics as well as alterations that may lead to the neurotoxic actions of ethanol.

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