Interleukin-6 -174G>C polymorphism and risk of coronary heart disease in West of Scotland Coronary Prevention Study (WOSCOPS)
Interleukin-6 -174G>C polymorphism and risk of coronary heart disease in West of Scotland Coronary Prevention Study (WOSCOPS)
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DOI：
10.1161/01.atv.0000013283.84306.1a
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发表时间：
2002-04-01
影响因子：
8.7
通讯作者：
Humphries, SE
中科院分区：
文献类型：
--
作者：
Basso, F;Lowe, GDO;Humphries, SE
白介素（IL）-6在冠心病（CHD）的发病机制中发挥着重要作用。已鉴定出 IL-6 启动子中的两个功能多态性（-174G>C 和 -572G>C），这两种罕见等位基因都与搭桥手术后较高的血浆 IL-6 水平相关，其中一个（-174G>C）与 CHID 风险相关。我们在苏格兰西部冠状动脉预防研究 (WOSCOPS) 中研究了这些多态性对 CHID 风险的贡献，这是一项一级预防试验，证明了普伐他汀在降低 CHID 的发病率和死亡率。对 498 例病例（包括在 4.8 年的随访期间经历心血管事件的个体）和 1109 名对照者（与年龄和吸烟习惯相匹配的个体）进行了基因分型。在安慰剂组中。与 GG+GC 组相比，没有显着证据表明 -174CC 基因型相关的风险更高。然而，在普伐他汀治疗组中，与 GG+GC 安慰剂组相比，CC 纯合子患 CHD 的风险显着降低（比值比 0.46。95% Cl 0.27 至 0.79）。在调整经典风险因素后，这一点在统计上仍然显着。与 GG+GC 组相比，CC 基因型的男性有一定程度的变化，但并不显着。他汀类药物治疗后，IL-6、C-反应蛋白或纤维蛋白原的基线水平较高，但 LDL 胆固醇显着下降（P=0.036）。 -572G>C 多态性与任何血浆性状或 CHD 风险均无显着相关性。因此，在接受普伐他汀治疗的受试者中，-174CC 基因型与较低的 CHID 风险相关。这些结果证明了炎症系统在确定 CHID 风险中的重要性，并支持他汀类药物对风险的非脂质作用。
Interleukin (IL)-6 plays an important role in the pathogenesis of coronary heart disease (CHD). Two functional polymorphisms in the IL-6 promoter have been identified (-174G>C and -572G>C), with both the rare alleles being associated with higher plasma levels of IL-6 after bypass surgery and one of them (-174G>C) associated with CHID risk, We have studied the contribution of these polymorphisms to CHID risk in the West of Scotland Coronary Prevention Study (WOSCOPS), a primary prevention trial that demonstrated the effectiveness of pravastatin in reducing morbidity and mortality from CHID. Four hundred ninety-eight cases (consisting of individuals experiencing a cardiovascular event during 4.8 years of follow-up) and 1109 controls (individuals matched for age and smoking habits) were genotyped. In the placebo group. there was no significant evidence of higher risk associated with the -174CC genotype compared with the GG+GC group. However, in the pravastatin-treated group, CC homozygotes had a significantly lower risk of CHD compared with the GG+GC placebo group (odds ratio 0.46. 95% Cl 0.27 to 0.79). and this remained statistically significant after adjustment for classic risk factors. Compared with the GG+GC group, men with the CC genotype had modestly, but not significantly. higher baseline levels of IL-6, C-reactive protein, or fibrinogen but showed a significantly greater fall in LDL cholesterol with statin treatment (P=0.036). The -572G>C polymorphism was not significantly associated with any plasma trait or CHD risk. Thus, in subjects under pravastatin treatment, the -174CC genotype was associated with a lower risk of CHID. These results demonstrate the importance of the inflammatory system in determining the risk of CHID and support the nonlipid effect of statins on risk.