Two new polymorphisms in the regulatory region of the apolipoprotein E gene, -491 A/T and -427 T/C, have been reported to be associated with the risk of Alzheimer's disease (AD). Moreover, in vitro studies suggest that the two polymorphisms modulate the levels of apoE protein expression. We examined these two polymorphisms, as well as the MspI polymorphism in the LDL receptor gene, in a series of elderly patients with late-onset sporadic AD and in an age-matched control group but failed to find any kind of association between these genetic features and an increased risk of AD. In the same samples we investigated the relationships between various genotypes and plasma lipid levels. Since the well-known effect of the three-allelic APOE polymorphism on plasma lipid levels could mask the effect of other polymorphisms, the analyses were performed taking into account the APOE genotype. The two regulatory region polymorphisms had significant effects only on the apoE levels. The -427 TT homozygotes had lower, and the -491 AA homozygotes had higher levels of apoE than other genotypes. This result confirmed in vivo the already observed in vitro effects of -491 A/T and -427 T/C polymorphisms on APOE promoter transcription activity.
Copyright 2001 S. Karger AG, Basel