title: Hypomethylation of Interleukin-6 Promoter is Associated with the Risk of Coronary Heart Disease.
abstract: BACKGROUND
  Interleukin-6 (IL-6) is implicated in the pathogenesis of coronary heart disease (CHD), and IL-6 expression has associated with reduced DNA methylation of its gene promoter. However, there are no data on IL-6 promoter methylation and the risk of CHD.
  
  
  OBJECTIVE
  To examine whether IL-6 promoter methylation measured in blood leukocyte DNA is associated with CHD risk.
  
  
  METHODS
  A total of 212 cases with CHD and 218 controls were enrolled. Methylation at two CpG sites in IL-6 promoter was measured by bisulfite pyrosequencing, and the mean IL-6 methylation was calculated by averaging the methylation measures of the two CpGs.
  
  
  RESULTS
  Mean methylation level in IL-6 promoter in CHD cases was significantly lower than that in controls (p = 0.023). Logistic regression analysis showed that IL-6 methylation was inversely associated with the risk of CHD. The odds ratios (ORs) of CHD for subjects in the second and first (lowest) tertile of IL-6 methylation were 1.87 (95% CI = 1.10‑3.20) and 2.01 (95% CI = 1.19-3.38) (ptrend = 0.013), respectively, compared to subjects in the third (highest) tertile. The IL-6 hypomethylation-related risk estimates tended to be stronger for acute myocardial infarction (ptrend = 0.006). CpG position-specific analysis showed that hypomethylation of position 1 conferred a more pronounced increase in CHD risk than that of position 2.
  
  
  CONCLUSIONS
  These findings suggest that DNA hypomethylation of IL-6 promoter is associated with the increased risk for CHD, especially for acute myocardial infarction. The two distinct CpGs in IL-6 may contribute differently to the development of CHD.
authors.affiliation: Department of Emergency, Tongji Hospital, Tongji University, Shanghai, China.
authors.forename: Hong-Peng
authors.initials: HP
authors.lastname: Zuo
authors.affiliation: Department of Computed Tomography, Jilin Oilfield General Hospital, Songyuan, Jilin Province, China.
authors.forename: Ying-Yu
authors.initials: YY
authors.lastname: Guo
authors.affiliation: Department of Cardiology, Tongji Hospital, Tongji University, Shanghai, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Che
authors.affiliation: Department of Emergency, Tongji Hospital, Tongji University, Shanghai, China.
authors.forename: Xian-Zheng
authors.initials: XZ
authors.lastname: Wu
mesh_terms: D000368:Aged; D000789:Angina, Unstable / Q000235:genetics; D003327:Coronary Disease / Q000235:genetics*; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics* / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D009203:Myocardial Infarction / Q000235:genetics; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA
chemical_list: D015850:Interleukin-6