IL-6 Receptor Polymorphisms May Be Associated With Aortic Aneurysm Risk

In a phenome-wide association study published in JAMA Cardiology, researchers from the VA Million Veteran Program reported an association between interleukin 6 receptor (IL6R) single-nucleotide polymorphisms (SNPs) and a reduced risk for aortic aneurysm.

Electronic health record (EHR) data of 332,799 patients from the VA Million Veteran Program, a longitudinal cohort study, were collected for analysis. Specifically, the researchers extracted laboratory measurements and diagnostic codes that were mapped to phenotype groups. The investigators performed a phenome-wide association study via fitting logistic regression and linear regression models that tested for correlations of IL6R SNPs with 1342 phenotype groups and associations between IL6R SNPs and 26 laboratory measurements, respectively. The researchers replicated findings from the Veteran Program in cohorts from the UK Biobank (n=408,455) and Vanderbilt University Biobank (n=13,835).

Identification of the IL6R SNP in the Veteran Program cohort was associated with a significantly reduced risk for aortic aneurysm phenotypes (odds ratio [OR] 0.87; 95% CI, 0.84-0.93), findings of which were replicated in the UK Biobank cohort. Also, coronary atherosclerosis and ischemic heart disease (OR 0.95; 95% CI, 0.94-0.97) were additional phenotypes that demonstrated significant associations with IL6R SNP.

The reduced risk for coronary heart disease in the Veterans cohort was replicated in the UK Biobank cohort. Abdominal aortic aneurysm was the only phenotype associated with IL6R SNP that also demonstrated correlations with the polymorphism in both the UK Biobank and Vanderbilt University Biobank.

Limitations of the study included the lack of replication of more phenotypes as well as the use of a single SNP to study associations.

The researchers believe their findings of an association between different aneurysm sub-phenotypes with IL6R SNPs likely “suggest that the beneficial effects of IL6R antagonist therapy may extend beyond treatment for aneurysms associated with large vessel vasculitis.”

Reference

Cai T, Zhang Y, Ho Y-L, et al; VA Million Veteran Program. Association of interleukin 6 receptor variant with cardiovascular disease effects of interleukin 6 receptor blocking therapy: a phenome-wide association study [published online August 8, 2018]. JAMA Cardiol. doi:10.1001/jamacardio.2018.2287