State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Int J Cardiol. 2012 May 31;157(2):243-52. doi: 10.1016/j.ijcard.2011.12.098. Epub 2012 Jan 18.
We aim to investigate whether the association between circulating interleukin 6 (IL-6) levels and the risk for coronary artery disease (CAD) is robust and perhaps even causal by a meta-analysis implementing mendelian randomization approach with IL-6 gene G-174C polymorphism as an instrument.
Data were available from 19 articles encompassing 9417 CAD patients and 15982 controls. A random effects model was applied irrespectively of between-study heterogeneity, and publication bias was examined using a funnel plot and the corresponding statistics.
Overall, comparison of IL-6 gene alleles -174C with -174G had 4% increased risk for CAD (95% confidence interval [95% CI]: 0.97-1.10; P=0.285), accompanying marginal heterogeneity (I(2)=38.3%; P=0.033). This association was potentiated in dominant model as odds ratio (OR) reached 1.08 (95% CI: 0.96-1.22; P=0.204) and heterogeneity was significant (I(2)=58.4%; P<0.0005). Subgroup analysis by ethnicity indicated that carriers of -174C allele were associated with a 12% increased risk for CAD in prospective studies involving White populations (OR=1.12; 95% CI: 0.95-1.33; P=0.184), whereas the association in East Asians was remarkably reversed with 37-46% reduced risk. Relative to -174GG homozygotes, carriers of -174C allele had an overall 0.24 pg/ml high circulating IL-6 levels (P=0.047). The predicted OR for 1 pg/ml elevation in IL-6 levels was 1.60 (95% CI: 1.44-1.72; P<0.01) in prospective studies involving White populations. Publication biases were absent for all comparisons (P>0.1).
Our findings provided strong evidence on the causal association of circulating IL-6 levels with the development of CAD in White populations.
我们旨在通过使用白细胞介素 6（IL-6）基因 G-174C 多态性作为工具的孟德尔随机化方法进行荟萃分析，来研究循环白细胞介素 6（IL-6）水平与冠心病（CAD）风险之间的关联是否稳健，甚至可能具有因果关系。
数据来自包含 9417 例 CAD 患者和 15982 例对照的 19 篇文章。应用随机效应模型，无论研究之间是否存在异质性，均进行分析，并使用漏斗图和相应的统计学方法检查发表偏倚。
总体而言，与 -174G 等位基因相比，IL-6 基因 -174C 等位基因使 CAD 风险增加了 4%（95%置信区间[95%CI]：0.97-1.10；P=0.285），同时伴有边缘异质性（I(2)=38.3%；P=0.033）。在显性模型中，这种关联得到增强，比值比（OR）达到 1.08（95%CI：0.96-1.22；P=0.204），且异质性显著（I(2)=58.4%；P<0.0005）。按种族进行的亚组分析表明，在涉及白人人群的前瞻性研究中，携带 -174C 等位基因的个体患 CAD 的风险增加了 12%（OR=1.12；95%CI：0.95-1.33；P=0.184），而东亚人的关联则明显逆转，风险降低了 37-46%。与 -174GG 纯合子相比，携带 -174C 等位基因的个体的循环白细胞介素 6（IL-6）水平总体升高 0.24 pg/ml（P=0.047）。在涉及白人人群的前瞻性研究中，IL-6 水平升高 1 pg/ml 的预测 OR 为 1.60（95%CI：1.44-1.72；P<0.01）。所有比较均不存在发表偏倚（P>0.1）。
我们的研究结果为白人人群中循环白细胞介素 6（IL-6）水平与 CAD 发生发展之间的因果关系提供了有力证据。
