title: Association of interleukin-6 circulating levels with coronary artery disease: a meta-analysis implementing mendelian randomization approach.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  Our findings provided strong evidence on the causal association of circulating IL-6 levels with the development of CAD in White populations.
authors.affiliation: State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. niuwenquan@yahoo.cn
authors.forename: Wenquan
authors.initials: W
authors.lastname: Niu
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Yue
authors.initials: Y
authors.lastname: Qi
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Wu
authors.forename: Dingliang
authors.initials: D
authors.lastname: Zhu
authors.forename: Wei
authors.initials: W
authors.lastname: Jin
mesh_terms: D015415:Biomarkers / Q000097:blood; D003324:Coronary Artery Disease / Q000097:blood* / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D015850:Interleukin-6 / Q000097:blood* / Q000235:genetics*; D057182:Mendelian Randomization Analysis / Q000379:methods*; D011446:Prospective Studies; D012189:Retrospective Studies
chemical_list: D015415:Biomarkers; D015850:Interleukin-6