Causal Link for IL-6 Receptor, Coronary Heart Disease
(HealthDay News) – Genetic data indicate that the interleukin-6 receptor (IL6R) has a causal link with coronary heart disease.
Nadeem Sarwar, PhD, from the University of Cambridge in the United Kingdom, and colleagues conducted a meta-analysis of studies comprising 125,222 participants to investigate the Asp358Ala (rs2228145) variant in IL6R in relation to conventional risk factors and inflammatory biomarkers for coronary heart disease. The researchers found that, for every copy of 358Ala, there was an increased concentration of IL6R and interleukin-6, and a reduction in concentration of C-reactive protein. The risk of coronary heart disease was reduced by 3.4% for every 358Ala allele inherited.
To assess the efficacy and safety of IL6R inhibition for primary prevention of coronary heart disease, Daniel I. Swerdlow, from University College London, and colleagues applied the mendelian randomization principle using single nucleotide polymorphisms (SNPs) in IL6R. Based on 40 studies involving 133,449 individuals, the researchers found that a non-synonymous IL6R variant (rs8192284) correlated with increased circulating interleukin-6 concentration as well as reduced C-reactive protein and fibrinogen concentrations. Based on analysis of 25,458 coronary heart disease cases and 100,740 controls, the rs7529229 SNP of IL6R correlated with significantly decreased odds of coronary heart disease events.
"On the basis of genetic evidence in human beings, IL6R signaling seems to have a causal role in development of coronary heart disease. IL6R blockade could provide a novel therapeutic approach to prevention of coronary heart disease that warrants testing in suitably powered randomized trials," the authors write.
Authors from both studies disclosed financial ties to pharmaceutical companies, including GlaxoSmithKline, which partially funded the Swerdlow study; several authors from both studies disclosed involvement with patents related to inflammatory markers.