Effect of the APOE‐491A/T promoter polymorphism on apolipoprotein E levels and risk of Alzheimer disease: The Rotterdam Study |
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| Authors: | G. Roks M. Cruts J.J. Houwing‐Duistermaat B. Dermaut S. Serneels L.M. Havekes A. Hofman M.M.B. Breteler C. Van Broeckhoven C.M. van Duijn |
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| Affiliation: | 1. Department of Epidemiology and Biostatistics, Erasmus Medical Center Rotterdam, The Netherlands;2. Department of Neurology, St. Elisabeth Hospital, Tilburg, The Netherlands;3. Flanders Interuniversity Institute for Biotechnology (VIB), University of Antwerp (UIA), Department of Biochemistry, Antwerp, Belgium;4. TNO Prevention and Health, Gaubius Laboratory, Leiden, The Netherlands |
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| Abstract: | 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. © 2002 Wiley‐Liss, Inc. |
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| Keywords: | apolipoprotein E APOE Alzheimer disease |
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