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A more recent version of this article appeared on June 1, 2006

Papers In Press, published online ahead of print March 9, 2006
J. Lipid Res., doi:10.1194/jlr.M600033-JLR200
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Submitted on January 20, 2006
Revised on March 8, 2006
Accepted on March 9, 2006

Relations of apolipoprotein E promoter polymorphisms and haplotypes to plasma low-density and total cholesterol levels and markers of subclinical atherosclerosis in the 21-year follow-up of the the cardiovascular risk in Young Finns study

Leena E. Viiri, Olli T. Raitakari, Heini Huhtala, Mika Kähönen, Riikka Rontu, Markus Juonala, Nina Hutri-Kähönen, Jukka Marniemi, Jorma S. A. Viikari, Pekka J. Karhunen, and Terho Lehtimäki

Department of Medicine, University of Tampere, Tampere 33014

Corresponding Author: leena.viiri{at}uta.fi

The common apolipoprotein E gene (APOE) e2/e3/e4 polymorphism explains part of serum lipid variation, and polymorphisms in the APOE promoter region have been proposed to participate in the regulation of serum lipid levels within the most common APOE e3/e3 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 e3/e3 carriers. We found no significant association between the APOE promoter genotypes and serum lipids (LDL-C, HDL-C, triglycerides), apolipoproteins (apoAI and apoB), or with brachial artery FMD, CAC or carotid IMT either in men or women. In longitudinal analyses in males, the carriers of heterozygous genotypes (-219G/T or +113G/C) and furthermore, carriers of –219T/+113C/e3 haplotype had statistically significantly higher LDL-C and total cholesterol (TC) concentrations throughout the 21-year follow-up period compared to homozygous G allele carriers or to non-carriers of the –219T/+113C/e3 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 TC concentrations in young Finnish males but do not seem to be major determinants for FMD, CAC or carotid IMT in males or females.


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