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Journal of Lipid Research, Vol. 47, 1298-1306, June 2006
Copyright © 2006 by American Society for Biochemistry and Molecular Biology

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

Leena E. Viiri^1,*, 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 Forensic Medicine, University of Tampere Medical School, and Centre for Laboratory Medicine, Tampere University Hospital, Tampere, Finland
Department of Clinical Physiology, University of Turku, Turku, Finland
Tampere School of Public Health, University of Tampere, Tampere, Finland
^** Department of Clinical Physiology, Tampere University Hospital, Tampere, Finland
Laboratory of Atherosclerosis Genetics, Department of Clinical Chemistry, Centre for Laboratory Medicine, University Hospital of Tampere, and Department of Clinical Chemistry, Tampere University Medical School, Tampere, Finland
Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland
^*** Department of Pediatrics, Tampere University Hospital, Tampere, Finland
Department of Health and Functional Capacity, Population Research Laboratory, National Public Health Institute, Turku, Finland
Department of Medicine, University of Turku, Turku, Finland

Published, JLR Papers in Press, March 9, 2006.

¹ To whom correspondence should be addressed. e-mail: leena.viiri{at}uta.fi

The common apolipoprotein E (apoE) gene (APOE) 2/3/4 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 3/3 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 3/3 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/3 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/3 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 females.

Supplementary key words lipid • intima-media thickness • flow-mediated dilatation • carotid artery compliance

Abbreviations: apoE, apolipoprotein E protein; APOE, apolipoprotein E gene; BMI, body mass index; CAC, carotid artery compliance; CRP, C-reactive protein; CV, coefficient of variation; FMD, flow-mediated dilatation; LDL-C, low density lipoprotein-cholesterol; IMT, intima-media thickness

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