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Original Articles

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

Leena E. Viiri, PhD; Keijo M. Viiri, MSc; Erkki Ilveskoski, MD, PhD; Heini Huhtala, MSc; Markku Mäki, MD, PhD; Pentti J. Tienari, MD, PhD; Markus Perola, MD, PhD; Terho Lehtimäki, MD, PhD and Pekka J. Karhunen, MD, PhD

From the Department of Forensic Medicine (L.E.V., E.I., P.J.K.), University of Tampere Medical School and Centre for Laboratory Medicine, Tampere University Hospital, Tampere, Finland; Paediatric Research Centre (K.M.V., M.M.), University of Tampere Medical School and Tampere University Hospital, Tampere, Finland; Heart Center (E.I.), Department of Cardiology, Pirkanmaa Hospital District, Tampere, Finland; Tampere School of Public Health (H.H.), University of Tampere, Tampere, Finland; Department of Neurology (P.J.T.), Helsinki University Central Hospital, University of Helsinki, Biomedicum Helsinki, Molecular Neurology Programme C522b, Helsinki, Finland; National Public Health Institute (M.P.), Department of Molecular Medicine, Helsinki, Finland; and Laboratory of Atherosclerosis Genetics (T.L.), Department of Clinical Chemistry, Centre for Laboratory Medicine, University Hospital of Tampere and Tampere University Medical School, Department of Clinical Chemistry, Tampere, Finland.

Correspondence to Leena E. Viiri, Department of Forensic Medicine, School of Medicine, 33014 University of Tampere, Tampere, Finland. E-mail Leena.Viiri{at}uta.fi

Received May 13, 2008; accepted September 29, 2008.

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 the 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 with G/G (12.7% versus 5.9%, P=0.007; 12.9% versus 6.3%, P=0.010, respectively) within nonsmokers. Within smokers, the associations were inverse. Moreover, smoking increased the fatty streak area within –219G/G or +113G/G genotypes and –219G/+113G/3 haplotype carriers. Functional studies in reporter assay showed that in comparison with 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 polymorphism has an effect on transcriptional activity.

Key Words: apolipoprotein • death, sudden • genetic transcription • genetics • lesion • smoking

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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]