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Apolipoprotein E polymorphism, homocysteine serum levels and hippocampal volume in patients with alcoholism: an investigation of a gene-environment interaction.

Wilhelm J, Frieling H, von Ahsen N, Hillemacher T, Kornhuber J, Bleich S

Department of Psychiatry and Psychotherapy, University of Erlangen-Nuremberg, Erlangen, Germany. julia.wilhelm@uk-erlangen.de

There is growing evidence that disadvantageous influences of the apolipoprotein E4 allele in the central nervous system are modified by environmental and dietary conditions. The present study investigated the gene-environment interaction of apolipoprotein E4 with homocysteine serum levels in patients with alcohol dependence with regard to alcohol-related hippocampal volume loss using volumetric high-resolution magnetic resonance imaging. We included 52 patients with alcohol-dependence. ApoE genotypes, homocysteine serum levels and hippocampal volumes were determined. We found a significant impact of homocysteine (F=13.2; df=1; P<0.001; 1-beta=0.95), not for ApoE4 genotype (F=0.482; df=1; P=0.49; 1-beta=0.05) on hippocampal volume. There was a significant interaction between both factors (ApoE4 x Hcy; F=8.8; df=1; P=0.005; 1-beta=0.80). The ApoE4 allele constitutes a risk factor for hippocampal volume loss in patients with alcohol dependence under the conditions of hyperhomocysteinemia. We suggest that the disadvantageous effects of apolipoprotein E4 on alcohol-related brain volume loss are based on certain gene-environment interactions.

Published 19 March 2008 in Pharmacogenomics J, 8(2): 117-21.
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