Department of Biochemistry, Research Laboratory, Rabta University Hospital & Elmanar University, 1007 Jabbari, Tunis, Tunisia.
Nutr Res. 2012 May;32(5):342-6. doi: 10.1016/j.nutres.2012.03.013. Epub 2012 Apr 27.
Many studies have shown that hyperhomocysteinemia may be an independent risk factor for coronary artery disease. However, not all prospective studies support an association between elevated plasma homocysteine levels and coronary artery disease. Nitric oxide (NO) plays a relevant role in various events during atherogenesis, and in vitro data suggest that NO may modulate total homocysteine (tHcy) concentrations, whereas polymorphisms of the endothelial nitric oxide (NOS3) gene have been reported to be related to an increased risk of myocardial infarction (MI) and hyperhomocysteinemia, but the results have been controversial. We hypothesized that the NOS3 synthase 4a4b VNTR polymorphism is a determinant of tHcy concentrations and tested this in 310 patients with MI and 250 controls. The NOS3 gene intron 4a4b VNTR polymorphism was analyzed by polymerase chain reaction analysis. There was no significant difference in the homocysteine levels between patients with MI and controls. The frequencies of the NOS34b4b, 4b4a, and 4a4a genotypes in the MI group were significantly different from those in the control group. In patients with MI, plasma tHcy concentrations were significantly different among the NOS3 genotypes (13.5±4.5, 18.5±3.9, and 20.4±2.1 μmol/L for 4b4b, 4a4b, and 4a4a genotypes, respectively; P<.001). However, no significant difference was observed for tHcy concentrations in the control group. In conclusion, the NOS34a4b gene polymorphism (presence of 4a allele) is associated with MI and influences plasma tHcy concentrations in patients with MI in the Tunisian male population.
许多研究表明高同型半胱氨酸血症可能是冠心病的一个独立危险因素。然而，并非所有前瞻性研究都支持血浆同型半胱氨酸水平升高与冠心病之间存在关联。一氧化氮（NO）在动脉粥样硬化形成过程中的各种事件中发挥着重要作用，体外数据表明，NO 可能调节总同型半胱氨酸（tHcy）浓度，而内皮型一氧化氮合酶（NOS3）基因的多态性已被报道与心肌梗死（MI）和高同型半胱氨酸血症的风险增加相关，但结果存在争议。我们假设 NOS3 合酶 4a4bVNTR 多态性是 tHcy 浓度的决定因素，并在 310 名 MI 患者和 250 名对照者中对此进行了检测。通过聚合酶链反应分析，对 NOS3 基因内含子 4a4bVNTR 多态性进行了分析。MI 组和对照组之间的同型半胱氨酸水平无显著差异。MI 组 NOS34b4b、4b4a 和 4a4a 基因型的频率与对照组有显著差异。在 MI 患者中，NOS3 基因型之间的血浆 tHcy 浓度有显著差异（4b4b、4a4b 和 4a4a 基因型分别为 13.5±4.5、18.5±3.9 和 20.4±2.1μmol/L；P<.001）。然而，对照组的 tHcy 浓度没有显著差异。总之，NOS34a4b 基因多态性（存在 4a 等位基因）与 MI 相关，并影响突尼斯男性人群中 MI 患者的血浆 tHcy 浓度。
