Relations of APOE promoter polymorphisms to LDL cholesterol and markers of subclinical atherosclerosis in young adults

Abstract

The common apolipoprotein E (apoE) gene (APOE) ε2/ε3/ε4 polymorphism explains part of serum lipid variation, and polymorphisms in the APOE promoter region have been proposed to participate in the regulation of serumlipid levels within the most common APOEε3/ε3 genotype group. We determined APOE -219G/T and +113G/C promoter genotypes and estimated APOE haplotypes in 525 participants of the Cardiovascular Risk in Young Finns Study. We studied the associations of the APOE promoter polymorphisms and their haplotypes with cross-sectional and longitudinal serum lipid and apolipoprotein concentrations as well as with flow-mediated dilatation (FMD), carotid artery compliance (CAC), and intima-media thickness (IMT) within the APOE ε3/ε3 carriers. We found no significant association between the APOE promoter genotypes and serum lipids [low density lipoprotein-cholesterol (LDL-C), HDL-C, and triglycerides], apolipoproteins (apoA-I and apoB), or brachial artery FMD, CAC, or carotid IMT in either men or women. In longitudinal analyses in males, the carriers of heterozygous genotypes (-219G/T or +113G/C) and, furthermore, carriers of the -219T/+113C/ε3 haplotype had significantly higher LDL-C and total cholesterol concentrations throughout the 21 year follow-up period compared with homozygous G allele carriers or noncarriers of the -219T/ +113C/ε3 haplotype. Such associations were not found in females. In summary, the APOE promoter polymorphisms -219G/T and +113G/C as well as their haplotype are associated with longitudinal changes in LDL-C and total cholesterol concentrations in young Finnish males but do not seem to be major determinants for FMD, CAC, or carotid IMT in males or female. Copyright © 2006 by the American Society for Biochemistry and Molecular Biology, Inc.