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. Conclusion: 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.

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Main Authors: Zuo,Hong-Peng, Guo,Ying-Yu, Che,Lin, Wu,Xian-Zheng
Format: Digital revista
Language:English
Published: Sociedade Brasileira de Cardiologia - SBC 2016
Online Access:http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0066-782X2016004100131
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spelling oai:scielo:S0066-782X20160041001312016-09-09Hypomethylation of Interleukin-6 Promoter is Associated with the Risk of Coronary Heart DiseaseZuo,Hong-PengGuo,Ying-YuChe,LinWu,Xian-Zheng Coronary Artery Disease Interleukin-6 DNA Methylation Epigenetic Repression 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. Conclusion: 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.info:eu-repo/semantics/openAccessSociedade Brasileira de Cardiologia - SBCArquivos Brasileiros de Cardiologia v.107 n.2 20162016-08-01info:eu-repo/semantics/articletext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S0066-782X2016004100131en10.5935/abc.20160124
institution SCIELO
collection OJS
country Brasil
countrycode BR
component Revista
access En linea
databasecode rev-scielo-br
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region America del Sur
libraryname SciELO
language English
format Digital
author Zuo,Hong-Peng
Guo,Ying-Yu
Che,Lin
Wu,Xian-Zheng
spellingShingle Zuo,Hong-Peng
Guo,Ying-Yu
Che,Lin
Wu,Xian-Zheng
Hypomethylation of Interleukin-6 Promoter is Associated with the Risk of Coronary Heart Disease
author_facet Zuo,Hong-Peng
Guo,Ying-Yu
Che,Lin
Wu,Xian-Zheng
author_sort Zuo,Hong-Peng
title Hypomethylation of Interleukin-6 Promoter is Associated with the Risk of Coronary Heart Disease
title_short Hypomethylation of Interleukin-6 Promoter is Associated with the Risk of Coronary Heart Disease
title_full Hypomethylation of Interleukin-6 Promoter is Associated with the Risk of Coronary Heart Disease
title_fullStr Hypomethylation of Interleukin-6 Promoter is Associated with the Risk of Coronary Heart Disease
title_full_unstemmed Hypomethylation of Interleukin-6 Promoter is Associated with the Risk of Coronary Heart Disease
title_sort hypomethylation of interleukin-6 promoter is associated with the risk of coronary heart disease
description 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. Conclusion: 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.
publisher Sociedade Brasileira de Cardiologia - SBC
publishDate 2016
url http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0066-782X2016004100131
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AT guoyingyu hypomethylationofinterleukin6promoterisassociatedwiththeriskofcoronaryheartdisease
AT chelin hypomethylationofinterleukin6promoterisassociatedwiththeriskofcoronaryheartdisease
AT wuxianzheng hypomethylationofinterleukin6promoterisassociatedwiththeriskofcoronaryheartdisease
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