Trompet S, de Craen A J M, Slagboom P, Shepherd J, Blauw G J, Murphy M B, Bollen E L E M, Buckley B M, Ford I, Gaw A, Macfarlane P W, Packard C J, Stott D J, Westendorp R G J, Jukema J W
Department of Cardiology, Leiden University Medical Centre, Leiden, The Netherlands.
Exp Gerontol. 2008 Aug;43(8):801-5. doi: 10.1016/j.exger.2008.04.006. Epub 2008 Apr 22.
Inflammation plays a prominent role in the development of atherosclerosis, which is the most important risk factor for vascular events. Lymphotoxin-alpha (LTA) is a pro-inflammatory cytokine and is found to be expressed in atherosclerotic lesions. We investigated the association between the C804A polymorphism within the LTA gene and coronary and cerebrovascular events in 5804 participants of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). The primary endpoint was the combined endpoint of death from coronary heart disease, non-fatal myocardial infarction, and clinical stroke. Secondary endpoints were the coronary and cerebrovascular components separately. All associations were assessed with a Cox-proportional hazards model adjusted for sex, age, pravastatin use, and country. Our overall analysis showed a significant association between the C804A polymorphism and the primary endpoint (p = 0.03). After stratification for gender, this association was found only in males. Furthermore, we found that the association between the C804A polymorphism and the primary endpoint was mainly attributable to clinical strokes (p = 0.02). The C804A polymorphism in the LTA gene associates with clinical stroke, especially in men. But further research is warranted to confirm our results.
炎症在动脉粥样硬化的发展过程中起着重要作用，而动脉粥样硬化是血管事件最重要的危险因素。淋巴毒素-α（LTA）是一种促炎细胞因子，在动脉粥样硬化病变中表达。我们在5804名高危老年人群普伐他汀前瞻性研究（PROSPER）的参与者中，研究了LTA基因内C804A多态性与冠状动脉和脑血管事件之间的关联。主要终点是冠心病死亡、非致命性心肌梗死和临床卒中的联合终点。次要终点分别是冠状动脉和脑血管事件。所有关联均采用Cox比例风险模型进行评估，并对性别、年龄、普伐他汀使用情况和国家进行了校正。我们的总体分析显示，C804A多态性与主要终点之间存在显著关联（p = 0.03）。按性别分层后，这种关联仅在男性中发现。此外，我们发现C804A多态性与主要终点之间的关联主要归因于临床卒中（p = 0.02）。LTA基因中的C804A多态性与临床卒中相关，尤其是在男性中。但需要进一步研究来证实我们的结果。
