Published Online
on October 15, 2008

A more recent version of this article appeared on December 1, 2008

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Original Article

Interactions of Functional APOE Promoter Polymorphisms with Smoking on Aortic Atherosclerosis

Leena E. Viiri^1,8; Keijo M. Viiri²; Erkki Ilveskoski³; Heini Huhtala⁴; Markku Mäki²; Pentti J. Tienari⁵; Markus Perola⁶; Terho Lehtimäki⁷ and Pekka J. Karhunen¹

¹ Dept. of Forensic Medicine, University of Tampere Medical School and Tampere University Hospital;
² Paediatric Research Centre, University of Tampere Medical School and Tampere University Hospital;
³ Dept. of Forensic Med., Univ.of Tampere Medical School and Heart Center, Pirkanmaa Hospital District;
⁴ Tampere School of Public Health, University of Tampere;
⁵ Department of Neurology, Helsinki University Central Hospital, University of Helsinki;
⁶ National Public Health Institute, Department of Molecular Medicine, Helsinki;
⁷ Laboratory of Atherosclerosis Genetics, Department of Clinical Chemistry, Centre for Laboratory Med

⁸ E-mail: leena.viiri{at}uta.fi

Background—Apolipoprotein E gene (APOE) interacts with environmental factors in defining risk for atherosclerosis. We studied whether the APOE 2/3/4 genotype or APOE promoter polymorphisms -219G/T and +113G/C might interact with smoking on the development of fatty streaks. We also studied the previously unknown effects of +113G/C on transcriptional activity.

Methods and Results—The fatty streak areas of aorta were measured morphometrically in subjects of Helsinki Sudden Death Study. Within APOE 3/3 subjects, there was a strong interaction between smoking and both -219G/T (p=0.009) and +113G/C (p=0.003) promoter polymorphisms on abdominal aorta fatty streak area: the -219T- and +113C-allele carriers had larger lesion areas compared to G/G (12.7% vs. 5.9%, p = 0.007; 12.9% vs. 6.3%, p = 0.010, respectively) within non-smokers. Within smokers the associations were inverse. Moreover, smoking increased the fatty streak area within -219G/G or +113G/G genotype and -219G/+113G/3 haplotype carriers. Functional studies in reporter assay showed that in comparison to the +113G-allele, the +113C-allele had higher transcriptional activity, and bound transcription factors from liver cell nuclear extract with significantly lower affinity.

Conclusions—In middle-aged Finnish men with APOE 3/3 genotype, the APOE promoter polymorphisms –219G/T and +113G/C interact with smoking in modulating aortic atherosclerosis. The +113G/C has an effect on transcriptional activity.

Key Words: apolipoproteins • death, sudden (if surviving, use heart arrest) • genetics • lesion • smoking

Related Article

Interactions of Functional Apolipoprotein E Gene Promoter Polymorphisms With Smoking on Aortic Atherosclerosis

Leena E. Viiri, Keijo M. Viiri, Erkki Ilveskoski, Heini Huhtala, Markku Mäki, Pentti J. Tienari, Markus Perola, Terho Lehtimäki, and Pekka J. Karhunen
Circ Cardiovasc Genet 2008 1: 107-116. [Abstract] [Full Text] [PDF]