The Institute of Cardiology, The Catholic University, Rome, Italy.
J Cardiovasc Med (Hagerstown). 2010 Jan;11(1):20-5. doi: 10.2459/JCM.0b013e328330e9fb.
Acute coronary syndromes (ACS) and chronic stable angina represent extremes of the clinical spectrum of coronary artery disease (CAD). It is unknown whether genetic determinants affect the first clinical manifestation of CAD. We evaluated the role of the C(-260)T polymorphism in the promoter of the CD14-receptor gene, an important mediator of the inflammatory response to lipopolysaccharide.
CD14 C(-260)T polymorphism was assessed in 100 patients with an acute presentation of CAD (group 1), 66 patients with stable presentation (group 2) and 88 healthy people (group 3); all patients were whites. In addition, baseline sCD14 plasma levels, and interleukin-6 production by circulating monocytes after in-vitro stimulation with lipopolysaccharide (1 ng/ml) were assessed. T/T homozygosis was more frequent in group 1 (36%, P < 0.001 versus others). Interleukin-6 production was higher in T/T homozygotes (median 4092.4; range 387-10 582 pg/ml) than in C/T heterozygotes (median 2442, range 40.5-9625 pg/ml, P < 0.001) and C/C homozygotes (median 3277.5; range 374.4-6250 pg/ml, P < 0.001). At multivariate analysis, T/T homozygosis and interleukin-6 production were independent predictors of acute presentation of CAD.
The present study shows that genetic factors that influence the reactivity of inflammatory cells may play a role in determining the first clinical presentation of CAD.
急性冠状动脉综合征（ACS）和慢性稳定型心绞痛代表了冠状动脉疾病（CAD）临床谱的两个极端。目前尚不清楚遗传因素是否会影响 CAD 的首次临床表现。我们评估了 CD14 受体基因启动子中的 C(-260)T 多态性在炎症反应中的作用，该基因是对脂多糖的重要介导物。
评估了 100 例急性 CAD 患者（第 1 组）、66 例稳定型患者（第 2 组）和 88 例健康人（第 3 组）中 CD14 C(-260)T 多态性；所有患者均为白人。此外，评估了基线 sCD14 血浆水平和循环单核细胞在体外用脂多糖（1ng/ml）刺激后产生的白细胞介素-6。T/T 纯合子在第 1 组中更为常见（36%，P<0.001 与其他组相比）。T/T 纯合子的白细胞介素-6 产生量较高（中位数 4092.4；范围 387-10582pg/ml），高于 C/T 杂合子（中位数 2442，范围 40.5-9625pg/ml，P<0.001）和 C/C 纯合子（中位数 3277.5；范围 374.4-6250pg/ml，P<0.001）。多变量分析显示，T/T 纯合子和白细胞介素-6 产生是急性 CAD 表现的独立预测因子。
本研究表明，影响炎症细胞反应性的遗传因素可能在决定 CAD 的首次临床表现中起作用。
