Stengård J H, Frikke-Schmidt R, Tybjaerg-Hansen A, Nordestgaard B G, Sing C F
Department of Epidemiology and Health Promotion, National Public Health Institute, Mannerheimintie 166 FIN-00300, Helsinki, Finland.
Ann Hum Genet. 2007 Nov;71(Pt 6):762-71. doi: 10.1111/j.1469-1809.2007.00370.x. Epub 2007 May 29.
The objective of this study was to evaluate whether an increased hazard of developing ischemic heart disease (IHD) is associated with any of the three genotypes A560T832/A560T832, A560T832/A560G832 and A560T832/T560T832, defined by variations in two non-coding SNPs in the 5' promoter region of the apolipoprotein E (APOE) gene. These genotypes were selected because they distinguished between high and low levels of HDL-C, TG and/or T-C in our earlier study of multiple samples defined by gender and population. We found a significant increase (p<0.05) in the hazard of IHD in females with the A560T832/T560T832 genotype that remained significant after fitting the effects of dyslipidemia, other established risk factors, and the structural isoform variations of the ApoE molecule. We discuss why this statistically significant genetic predictor may not be an appropriate screening test for IHD in the Danish population at large.
本研究的目的是评估患缺血性心脏病（IHD）风险的增加是否与载脂蛋白E（APOE）基因5'启动子区域两个非编码单核苷酸多态性（SNP）变异所定义的三种基因型A560T832/A560T832、A560T832/A560G832和A560T832/T560T832中的任何一种相关。选择这些基因型是因为在我们早期对按性别和人群定义的多个样本的研究中，它们区分了高密度脂蛋白胆固醇（HDL-C）、甘油三酯（TG）和/或总胆固醇（T-C）的高低水平。我们发现，携带A560T832/T560T832基因型的女性患IHD的风险显著增加（p<0.05），在考虑血脂异常、其他既定风险因素以及载脂蛋白E分子的结构异构体变异的影响后，这一结果仍然显著。我们讨论了为什么这种具有统计学意义的基因预测指标可能不适用于丹麦总体人群的IHD筛查。
