The apolipoprotein E (APOE) gene is involved in lipid transport. A common polymorphism in this gene with the APOE*2, APOE*3, and APOE*4 alleles influences plasma levels of apolipoprotein E and cholesterol. Besides its role in lipid transport, the APOE*4 allele is a genetic risk factor for Alzheimer disease (AD). Recently, a polymorphism in the APOE promoter region was found to be involved in plasma apolipoprotein E levels and was found associated with AD. We studied the effect of this -491A/T promoter polymorphism on plasma apolipoprotein E levels and risk for AD in a population-based case-control study. We found that there was a modest but statistically significant effect of the -491A/T polymorphism on plasma apolipoprotein E levels independent of the APOE genotype. The lowest plasma levels were measured for the AA genotype, highest levels for the TT genotype, and intermediate levels for the heterozygotes. There was a small effect of the -491 AA genotype on AD risk that disappeared after adjusting for APOE genotypes. Our data suggest that the -491A/T polymorphism has an APOE genotype-independent effect on plasma apolipoprotein E levels but no APOE-independent effect on AD risk.

Alzheimer disease, APOE, Apolipoprotein E
dx.doi.org/10.1002/ajmg.10407, hdl.handle.net/1765/61596
American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics
Erasmus MC: University Medical Center Rotterdam

Roks, C.M.A.A, Cruts, M, Houwing-Duistermaat, J.J, Dermaut, B, Serneels, S, Havekes, L.M, … van Duijn, C.M. (2002). Effect of the APOE-491A/T promoter polymorphism on apolipoprotein E levels and risk of Alzheimer disease: The Rotterdam Study. American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics, 114(5), 570–573. doi:10.1002/ajmg.10407