Interleukin-6 receptor pathways in coronary heart disease: a collaborative meta-analysis of 82 studies
The Lancet - Early Online Publication, 04/09/2012
Large–scale human genetic and biomarker data are consistent with a causal association between IL6R–related pathways and coronary heart disease.Methods
- In a collaborative meta–analysis, the authors studied Asp358Ala (rs2228145) in IL6R in relation to a panel of conventional risk factors and inflammation biomarkers in 125 222 participants.
- The authors also compared the frequency of Asp358Ala in 51 441 patients with coronary heart disease and in 136 226 controls.
- To gain insight into possible mechanisms, the authors assessed Asp358Ala in relation to localised gene expression and to postlipopolysaccharide stimulation of interleukin 6.
- The minor allele frequency of Asp358Ala was 39%.
- Asp358Ala was not associated with lipid concentrations, blood pressure, adiposity, dysglycaemia, or smoking (p value for association per minor allele ≥0.04 for each).
- By contrast, for every copy of 358Ala inherited, mean concentration of IL6R increased by 34.3% (95% CI 30•4—38.2) and of interleukin 6 by 14•6% (10.7—18•4), and mean concentration of C–reactive protein was reduced by 7.5% (5.9—9.1) and of fibrinogen by 1.0% (0.7—1.3).
- or every copy of 358Ala inherited, risk of coronary heart disease was reduced by 3.4% (1.8—5.0).
- Asp358Ala was not related to IL6R mRNA levels or interleukin–6 production in monocytes.