Colombo Maria Giovanna, Paradossi Umberto, Andreassi Maria Grazia, Botto Nicoletta, Manfredi Samantha, Masetti Serena, Biagini Andrea, Clerico Aldo
CNR Institute of Clinical Physiology, G. Pasquinucci Hospital, Via Aurelia SUD-Montepepe, 54100 Massa, Italy.
Clin Chem. 2003 Mar;49(3):389-95. doi: 10.1373/49.3.389.
Endothelial nitric oxide synthase (eNOS) could be a candidate gene for coronary artery disease (CAD). This study investigated the relationship of the eNOS Glu(298)-->Asp and T(786)-->C polymorphisms with the presence and severity of CAD in the Italian population.
We enrolled 415 unrelated individuals who underwent coronary angiography. The severity of CAD was expressed by means of the Duke score. The eNOS Glu(298)-->Asp and T(786)-->C variants were analyzed by PCR.
There was significant linkage disequilibrium between the two eNOS polymorphisms (P <0.0001). Both variants were significantly associated with the occurrence and severity of CAD (P = 0.01 and 0.004 for Glu(298)-->Asp and T(786)-->C, respectively). The risk of CAD was increased among individuals homozygous for the C allele of the T(786)-->C polymorphism compared with individuals homozygous for the T allele (odds ratio = 2.5; P <0.01) and was independent of the other common risk factors (P = 0.04). Moreover, individuals with both the Asp/Asp genotype of the Glu(298)-->Asp polymorphism and at least one C allele of the T(786)-->C variant in the promoter region of the eNOS gene had an increased risk of CAD (odds ratio = 4.0; P <0.001) and a significantly higher mean Duke score (26.2 +/- 2.9 vs 45.2 +/- 3.7; P = 0.002) compared with individuals with the TT genotype and the Glu allele.
The present study provides evidence that the Glu(298)-->Asp and T(786)-->C polymorphisms of the eNOS gene are associated with the presence and severity of angiographically defined CAD in the Italian population and that those individuals carrying both eNOS variants simultaneously might have a higher risk of developing CAD.
内皮型一氧化氮合酶（eNOS）可能是冠状动脉疾病（CAD）的候选基因。本研究调查了意大利人群中eNOS基因Glu(298)→Asp和T(786)→C多态性与CAD的存在及严重程度之间的关系。
我们纳入了415名接受冠状动脉造影的无亲缘关系个体。CAD的严重程度用杜克评分表示。通过聚合酶链反应（PCR）分析eNOS基因Glu(298)→Asp和T(786)→C变异。
两种eNOS多态性之间存在显著的连锁不平衡（P<0.0。两种变异均与CAD的发生及严重程度显著相关（Glu(298)→Asp和T(786)→C分别为P = 0.01和0.004）。与T等位基因纯合个体相比，T(786)→C多态性的C等位基因纯合个体患CAD的风险增加（比值比 = 2.5；P<0.01），且独立于其他常见风险因素（P = 0.04）。此外，与TT基因型和Glu等位基因个体相比，eNOS基因启动子区域Glu(298)→Asp多态性的Asp/Asp基因型且T(786)→C变异至少有一个C等位基因的个体患CAD的风险增加（比值比 = 4.0；P<0.001），且平均杜克评分显著更高（26.2±2.9对45.2±3.7；P = 0.002）。
本研究提供了证据表明，eNOS基因的Glu(298)→Asp和T(786)→C多态性与意大利人群中血管造影定义的CAD的存在及严重程度相关，且同时携带两种eNOS变异的个体可能有更高的患CAD风险。
