Brain, Vol. 123, No. 3, 585-590,
March 2000
© 2000 Oxford University Press
Invited review |
The impact of apolipoprotein E genotypes on age at onset of symptoms and phenotypic expression in Wilson's disease
1 Departments of Clinical Neurology and 2 Internal Medicine IV, Gastroenterology and Hepatology, University of Vienna, Vienna, Austria and 3 Departments of Internal Medicine II and 4 Neurology, University of Leipzig, Leipzig, Germany
Correspondence to:
Professor Harald Kollegger, MD, Department of Clinical Neurology, University of Vienna, Währinger Gürtel 18–20, A-1090 Vienna, Austria E-mail: harald.kollegger{at}univie.ac.at
Wilson's disease is a disorder of biliary copper excretion that may result in severe neurological symptoms and advanced liver disease. The wide variation of phenotypic disease expression cannot be fully explained by the different mutations of the Wilson disease gene. In neurological disorders, such as Alzheimer's disease, temporal lobe epilepsy and cerebral trauma, the presence of the apolipoprotein E (ApoE) allele 
4 is associated with an increased vulnerability of the brain to the effects of the disease, whereas the presence of the ApoE genotype 3/3 appears to provide moderate neuroprotection. We examined whether this hypothesis holds true for the development of neurological symptoms in patients with Wilson's disease. The ApoE genotype and the H1069Q mutation (the most common in Wilson's disease) status were determined by polymerase chain reaction-based mutation assays in 121 well-characterized, symptomatic index patients with Wilson's disease. An investigation profile was established in which the patients were grouped according to the clinical symptoms at presentation, the ApoE genotypes and the status of the H1069Q mutation. Fifty-nine per cent of the 121 patients had the allele combination ApoE 3/3 (21% ApoE 3/4, 19% ApoE 3/2, 1% ApoE 4/2). The distribution of ApoE genotypes did not deviate from known distributions in healthy European subjects. Within the group of 40 H1069Q-homozygous patients, the onset of symptoms was significantly delayed in patients with the ApoE 3/3 genotype (25 ± 6 years at presentation) compared with patients with the ApoE 3/4 genotype (20 ± 3 years at presentation). In this study, the ApoE genotype was established as an important factor delaying the onset of neurological and hepatic symptoms, but not modifying phenotypic disease expression in a homogenous group of patients with Wilson's disease (all H1069Q-homozygotes, similar genetic background). The presence of ApoE 3/3 attenuates clinical manifestations in Wilson's disease by mechanisms which might involve the antioxidant and membrane-stabilizing properties of the ApoE 3 protein.
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