Application of DNA microarrays to study human alcoholism

An emerging idea is that long-term alcohol abuse results in changes in gene expression in the brain and that these changes are responsible at least pa rtly for alcohol tolerance, dependence and neurotoxicity, The overall goal of our research is to identify genes which are differentia[ly expressed in the brains of well-characterized human alcoholics as compared with non-alco holics. This should identify as-yet-unknown alcohol-responsive genes, and m ay well confirm changes in the expression of genes which have been delineat ed in animal models of alcohol abuse. Cases were carefully selected and sam ples pooled on the basis of relevant criteria; differential expression was monitored by microarray hybridization. The inherent diversity of human alco holics can be exploited to identify genes associated with specific patholog ical processes, as well as to assess the effects of concomitant disease, se verity of brain damage, drinking behavior, and factors such as gender and s moking history. initial results show selective changes in gene expression i n alcoholics; of particular importance is a coordinated reduction in genes coding for myelin components, Copyright (C) 2001 National Science Council, ROC and S. Karger AG, Basel.