The interleukin-6-174 G/C promoter polymorphism is associated with risk of coronary heart disease and systolic blood pressure in healthy men
The interleukin-6-174 G/C promoter polymorphism is associated with risk of coronary heart disease and systolic blood pressure in healthy men
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DOI：
10.1053/euhj.2001.2678
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发表时间：
2001-12-01
影响因子：
39.3
通讯作者：
Miller, GJ
中科院分区：
文献类型：
--
作者：
Humphries, SE;Luong, LA;Miller, GJ
炎症是冠心病的重要组成部分，编码细胞因子的基因是冠心病易感基因。我们在2751名健康的英国中年人中检测了白细胞介素-6（IL-6）基因启动子的两种多态性（-174G >C和-572G >C）对冠心病风险的影响，以及对包括纤维蛋白原和收缩压在内的中等风险特征的影响。结果-174C等位基因在男性中的分布频率高于男性（频率0.43，95% CI 0.42-0.44）与纤维蛋白原水平的显著影响无关，但与纤维蛋白原水平的显著影响相关。（P=0.007）收缩压升高（平均mmHg（95% CI）：GG=135.5（134.3-136.7）; GC=137.9（136.9-138.9）; CC=138.0（136.3-139.8））。这种影响在吸烟者和非吸烟者中的程度相似，在体重指数最高的两个三分位数（> 24.86 kg）的男性中更大。m（-2））比在底部三分位数的那些。与GG基因型相比，携带-174C等位基因的男性患冠心病的相对危险度为1.54（95%CI 1.0-2.23，P=0.048），吸烟者的影响最大（与GG非吸烟者相比，RR 2.66，CI 1.64-4.32）。在调整包括血压在内的经典风险因素后，这些影响仍具有统计学显著性（P=0.04）。-572C等位基因（频率0.05，0.04-0.06）与血压，纤维蛋白原或冠心病的相对风险的显着影响无关。在一组基因型男性（n=494）中，-174 C等位基因携带者的C反应蛋白水平高于非携带者。结论这些数据证实了炎症系统在冠心病发展中的重要性。他们认为，至少部分地，IL-6 - 174 G>C多态性对血压的影响可能是通过炎症机制起作用的，但基因型对冠心病风险的影响在很大程度上无法通过其对血压的影响来解释。遗传决定的IL-6血浆水平差异产生这些效应的分子机制仍有待确定。(C)2001年欧洲心脏病学会。
Aims Inflammation is a key component of coronary heart disease, and genes coding for cytokines are candidates for predisposing to coronary heart disease risk. We have examined the effect of two polymorphisms (-174G >C and -572G >C) in the promoter of the interleukin-6 (IL-6) gene on risk of coronary heart disease, and on intermediate risk traits including fibrinogen and systolic blood pressure, in 2751 middle-aged healthy U.K. men.Results The -174C allele (frequency 0.43, 95% Cl 0.42-0.44) was not associated with significant effects on fibrinogen levels, but was associated with a significantly (P=0.007) higher systolic blood pressure (mean mmHg (95% Cl): GG=135.5 (134.3-136.7); GC=137.9 (136.9-138.9); CC=138.0 (136.3-139.8)). This effect was of similar magnitude in smokers and non-smokers, and was greater in men in the top two tertiles of body mass index (> 24.86 kg . m(-2)) than in those in the bottom tertile. Compared to those with the genotype GG, men carrying the -174C allele had a relative risk of coronary heart disease of 1.54 (95% CI 1.0-2.23, P=0.048) and this effect was greatest in smokers (compared to GG non-smokers, RR 2.66, Cl 1.64-4.32). These effects remained statistically significant after adjusting for classical risk factors including blood pressure (P=0.04). The -572C allele (frequency 0.05, 0.04-0.06) was not associated with a significant effect on blood pressure, fibrinogen or relative risk of coronary heart disease. In a subset of the genotyped men (n=494), carriers of the -174C allele had hi-her levels of C-reactive protein than non-carriers.Conclusions These data confirm the importance of the inflammatory system in the development of coronary heart disease. They suggest that, at least in part, the effect of the IL-6 -174G >C polymorphism on blood pressure is likely to be operating through inflammatory mechanisms, but the genotype effect on coronary heart disease risk is largely unexplained by its effect on blood pressure. The molecular mechanisms whereby genetically determined differences in plasma levels of IL-6 are having these effects remain to be determined. (C) 2001 The European Society of Cardiology.