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Association of interleukin-6 circulating levels with coronary artery disease: a meta-analysis implementing mendelian
1State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. niuwenquan@yahoo.cn
Insights
Interleukin 6 (IL-6) levels are causally linked to coronary artery disease (CAD) risk in White populations. This meta-analysis used a Mendelian randomization approach to confirm the association between IL-6 and CAD development.
Area of Science:
- Genetics and Cardiovascular Medicine
- Inflammation and Immunology
Background:
- Circulating interleukin 6 (IL-6) levels are implicated in cardiovascular health.
- The causal relationship between IL-6 and coronary artery disease (CAD) requires robust investigation.
Purpose of the Study:
- To investigate the causal association between circulating IL-6 levels and CAD risk.
- Utilize a meta-analysis with a Mendelian randomization approach, employing the IL-6 gene G-174C polymorphism as an instrumental variable.
Main Methods:
- Meta-analysis of 19 articles including 9417 CAD patients and 15982 controls.
- Random effects model applied irrespective of heterogeneity.
- Publication bias assessed using funnel plots and associated statistics.
Main Results:
- The IL-6 gene -174C allele showed a 4% increased risk for CAD overall (OR=1.04, P=0.285).
- Subgroup analysis revealed a 12% increased CAD risk in White populations (OR=1.12, P=0.184) but a reduced risk in East Asians.
- Elevated IL-6 levels (0.24 pg/ml) were associated with the -174C allele, predicting a 1.60 odds ratio for CAD per 1 pg/ml IL-6 increase in Whites.
Conclusions:
- Strong evidence supports a causal association between circulating IL-6 levels and CAD development in White populations.
- Mendelian randomization confirms IL-6 as a potential causal factor for CAD in specific ethnic groups.
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).
Conclusion:
Our findings provided strong evidence on the causal association of circulating IL-6 levels with the development of CAD in White populations.
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