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

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.