Viiri Leena E, Viiri Keijo M, Ilveskoski Erkki, Huhtala Heini, Mäki Markku, Tienari Pentti J, Perola Markus, Lehtimäki Terho, Karhunen Pekka J
Department of Forensic Medicine, University of Tampere Medical School and Centre for Laboratory Medicine, Tampere University Hospital, Tampere, Finland.
Circ Cardiovasc Genet. 2008 Dec;1(2):107-16. doi: 10.1161/CIRCGENETICS.108.791764. Epub 2008 Oct 15.
Apolipoprotein E gene (APOE) interacts with environmental factors in defining risk for atherosclerosis. We studied whether the APOE epsilon2/epsilon3/epsilon4 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.
The fatty streak areas of aorta were measured morphometrically in subjects of the Helsinki Sudden Death Study. Within APOE epsilon3/epsilon3 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/epsilon3 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.
In middle-aged Finnish men with APOE epsilon3/epsilon3 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.
载脂蛋白E基因（APOE）在确定动脉粥样硬化风险方面与环境因素相互作用。我们研究了APOE ε2/ε3/ε4基因型或APOE启动子多态性-219G/T和+113G/C是否可能与吸烟在脂肪条纹形成过程中相互作用。我们还研究了+113G/C对转录活性的此前未知的影响。
在赫尔辛基猝死研究的受试者中，通过形态计量学测量主动脉的脂肪条纹面积。在APOE ε3/ε3受试者中，吸烟与-219G/T（P=0.009）和+113G/C（P=0.003）启动子多态性在腹主动脉脂肪条纹面积上存在强烈相互作用：与非吸烟者中的G/G相比，-219T和+113C等位基因携带者的病变面积更大（分别为12.7%对5.9%，P=0.007；12.9%对6.3%，P=0.010）。在吸烟者中，关联则相反。此外，吸烟增加了-219G/G或+113G/G基因型以及-219G/+113G/ε3单倍型携带者的脂肪条纹面积。报告基因检测中的功能研究表明，与+113G等位基因相比，+113C等位基因具有更高的转录活性，并且与来自肝细胞核提取物的转录因子结合的亲和力显著更低。
在具有APOE ε3/ε3基因型的中年芬兰男性中，APOE启动子多态性-219G/T和+113G/C在调节主动脉粥样硬化方面与吸烟相互作用。+113G/C多态性对转录活性有影响。
