In:
Circulation: Cardiovascular Genetics, Ovid Technologies (Wolters Kluwer Health), Vol. 1, No. 2 ( 2008-12), p. 107-116
Abstract:
Background— Apolipoprotein E gene (APOE) interacts with environmental factors in defining risk for atherosclerosis. We studied whether the APOE ε2/ε3/ε4 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 ε3/ε3 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/ε3 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 ε3/ε3 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.
Type of Medium:
Online Resource
ISSN:
1942-325X
,
1942-3268
DOI:
10.1161/CIRCGENETICS.108.791764
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2008
detail.hit.zdb_id:
2927603-2
detail.hit.zdb_id:
2457085-0
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