title: 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.
authors.affiliation: a Department of Cardiology , the Fourth Affiliated Hospital, Harbin Medical University , Harbin , Heilongjiang , P. R. China ;
authors.forename: Qinghui
authors.initials: Q
authors.lastname: Yang
authors.affiliation: b Department of Cardiovascular Surgery , the Fourth Affiliated Hospital, Harbin Medical University , Harbin , Heilongjiang , P. R. China.
authors.forename: Yushi
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: b Department of Cardiovascular Surgery , the Fourth Affiliated Hospital, Harbin Medical University , Harbin , Heilongjiang , P. R. China.
authors.forename: Zhijie
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: b Department of Cardiovascular Surgery , the Fourth Affiliated Hospital, Harbin Medical University , Harbin , Heilongjiang , P. R. China.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Chen
mesh_terms: D056808:Biostatistics; D004247:DNA / Q000737:chemistry / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D004198:Disease Susceptibility; D004797:Enzyme-Linked Immunosorbent Assay; D057890:Epigenomics; D005260:Female; D015870:Gene Expression; D006801:Humans; D015850:Interleukin-6 / Q000097:blood / Q000737:chemistry* / Q000235:genetics*; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D017202:Myocardial Ischemia / Q000235:genetics*; D012307:Risk Factors; D015854:Up-Regulation / Q000235:genetics
chemical_list: D015850:Interleukin-6; D004247:DNA
keywords: DNA methylation; Disease susceptibility; epigenomics; gene expression; interleukin-6; myocardial ischemia