title: Apolipoprotein E polymorphism, homocysteine serum levels and hippocampal volume in patients with alcoholism: an investigation of a gene-environment interaction.
abstract: 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.
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Erlangen-Nuremberg, Erlangen, Germany. julia.wilhelm@uk-erlangen.de
authors.forename: J
authors.initials: J
authors.lastname: Wilhelm
authors.forename: H
authors.initials: H
authors.lastname: Frieling
authors.forename: N
authors.initials: N
authors.lastname: von Ahsen
authors.forename: T
authors.initials: T
authors.lastname: Hillemacher
authors.forename: J
authors.initials: J
authors.lastname: Kornhuber
authors.forename: S
authors.initials: S
authors.lastname: Bleich
mesh_terms: D000328:Adult; D000437:Alcoholism / Q000097:blood / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D053327:Apolipoprotein E4 / Q000235:genetics*; D004777:Environment; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006624:Hippocampus / Q000473:pathology*; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000097:blood / Q000150:complications*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009929:Organ Size; D011110:Polymorphism, Genetic; D012307:Risk Factors
chemical_list: D053327:Apolipoprotein E4; D006710:Homocysteine