Chen Qi, Reis Steven E, Kammerer Candace M, McNamara Dennis M, Holubkov Richard, Sharaf Barry L, Sopko George, Pauly Daniel F, Bairey Merz C Noel, Kamboh M Ilyas
Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, 130 De Soto Street, Pittsburgh, PA 15261, USA.
Atherosclerosis. 2003 Jul;169(1):159-67. doi: 10.1016/s0021-9150(03)00160-6.
Genetic variation in the apolipoprotein E (APOE) gene is a significant determinant of variation in plasma cholesterol levels and it also affects the risk of coronary artery disease (CAD). We examined the association of the APOE polymorphism with CAD severity in women from the NHLBI-sponsored Women's Ischemia Syndrome Evaluation (WISE) study. Quantitative coronary angiography was used to classify subjects as having normal/minimal CAD (<20% stenosis), mild CAD (20-49% stenosis) and significant CAD (>or=50% stenosis). The women with or=50% stenosis were further stratified according to the number of vessel disease they have (one, two, or three). In white subjects, the frequency of APOE4 carriers (3/4 and 4/4 genotypes) was significantly higher in the combined mild/significant CAD group (>or=20% stenosis) compared with the normal/minimal CAD group (<20% stenosis) (31.3 vs. 19.2%; P=0.025) with an adjusted OR of 2.40 (95% CI: 1.47-3.93; P=0.0005). Furthermore, the APOE4 allele was found to be significantly associated with the increased vessel disease number (chi(2)=8.04; P=0.0046). This association of the APOE4 allele with CAD severity was present only in women with family history of CAD. APOE polymorphism also showed significant associations with increasing plasma total cholesterol (P=0.01) and low-density lipoprotein (LDL)-cholesterol (P<0.001) in whites. These data support the hypothesis that the APOE4 allele is an independent risk factor not only for the presence of CAD and hyperlipidemia, but also for the angiographic severity of CAD in white women with a family history of disease.
载脂蛋白E（APOE）基因的遗传变异是血浆胆固醇水平变异的一个重要决定因素，并且它还影响冠状动脉疾病（CAD）的风险。我们在由美国国立心肺血液研究所（NHLBI）资助的女性缺血综合征评估（WISE）研究中，检测了APOE基因多态性与女性CAD严重程度之间的关联。采用定量冠状动脉造影将受试者分类为患有正常/轻度CAD（狭窄<20%）、轻度CAD（狭窄20%-49%）和重度CAD（狭窄≥50%）。狭窄≥50%的女性根据其患血管疾病的数量（一支、两支或三支）进一步分层。在白人受试者中，与正常/轻度CAD组（狭窄<20%）相比，轻度/重度CAD合并组（狭窄≥20%）中APOE4携带者（3/4和4/4基因型）的频率显著更高（31.3%对19.2%；P=0.025），校正后的比值比为2.40（95%可信区间：1.47-3.93；P=0.0005）。此外，发现APOE4等位基因与血管疾病数量增加显著相关（χ2=8.04；P=0.0046）。APOE4等位基因与CAD严重程度的这种关联仅在有CAD家族史的女性中存在。APOE基因多态性在白人中还与血浆总胆固醇升高（P=0.01）和低密度脂蛋白（LDL）胆固醇升高（P<0.001）显著相关。这些数据支持以下假说：APOE4等位基因不仅是CAD和高脂血症存在的独立危险因素，而且是有疾病家族史的白人女性CAD血管造影严重程度的独立危险因素。
