Association of interleukin-6 methylation in leukocyte DNA with serum level and the risk of ischemic heart disease

Abstract

Background Interleukin-6 (IL-6), a multifunctional cytokine, plays an important role in the development of ischemic heart disease (IHD), and DNA hypomethylation of 2 CpGs, located downstream in the proximity of the IL-6 gene promoter, has been associated with risk factor for IHD. This study was to examine the association of blood leukocyte DNA methylation of the 2 CpGs in IL-6 with the risk of IHD and the serum IL-6 level. Methods IL-6 methylation levels of 582 cases and 673 controls were measured using the bisulfite pyrosequencing technology. Serum level of IL-6 was measured using enzyme-linked immunosorbent assay. Results The IL-6 methylation was significantly lower in IHD cases than in the controls, irrespective of CpG site. After multivariate adjustment, lower (< median) average IL-6 methylation was associated with an increased risk of IHD (OR 1.57, 95% CI 1.22–2.02, p < 0.001). Average IL-6 methylation level was inversely associated with serum IL-6 level (β = −1.02 pg/mL per increase in IL-6 methylation, p = 0.002) among IHD cases. This significant relationship was not observed among controls. Conclusions DNA hypomethylation of IL-6 gene measured in blood leukocytes was associated with increased risk of IHD. IL-6 demethylation may upregulate its expression, whereby exerting its risk effect on the development of IHD.

Key Words:

• Disease susceptibility
• DNA methylation
• epigenomics
• gene expression
• interleukin-6
• myocardial ischemia

Acknowledgements

This study was supported by Heilongjiang Science Foundation for Young Scholar (No. QC2009C14).

Disclosure statement

The authors report no conflict of interest. The authors alone are responsible for the content and writing of the paper.