title: Hypomethylation of interleukin-6 (IL-6) gene increases the risk of essential hypertension: a matched case-control study.
abstract: Essential hypertension (EH) is a chronic disease with clear epigenetic component. Inflammation and endothelial dysfunction have a great role in the development of persistent blood pressure elevation. The aim of this study was to explore an association between EH and DNA methylation in pro-inflammation cytokine gene interleukin-6 (IL-6) during the inflammatory process. We performed methylation analysis of peripheral blood DNA using bisulphite pyrosequencing technology between 96 EH patients and 96 age- and gender-matched healthy controls. The present results showed that three cytosine-phosphate-guanine (CpG) sites of IL-6 promoter CpG island had different lower methylation in EH group compared with controls, but only CpG2 (58.43±7.53 versus 62.34±9.65, P=0.004) and CpG3 (51.52±6.18 versus 57.45±8.29, P<0.001) had statistical difference. Logistic regression analysis found CpG3 hypomethylation was a risk factor of EH (odds ratio=1.111, adjusted P=0.004). In addition, we found hypermethylation of CpG1 (64.84±7.06 versus 61.84±8.61) and CpG2 (62.04±7.40 versus 59.30±9.57) in male compared with female. In male, we found hypomethylation of CpG2 (60.41±7.74 versus 64.28±6.36) and CpG3 (53.70±8.62 versus 57.78±7.87) of smoker versus non-smoker and hypomethylation of CpG2 (60.89±7.32 versus 64.70±7.03) and CpG3 (53.23±7.99 versus 60.48±7.58) of drinker versus non-drinker. Furthermore, the CpG2 and CpG3 had a negative correlation with systolic blood pressure and diastolic blood pressure (P<0.05). Receiver operating characteristic curve analysis showed that CpG2 (area under curve: 0.638, P=0.001) and CpG3 (area under curve: 0.704, P<0.001) had a diagnostic value to predict the risk of EH. In summary, our study revealed hypomethylation of IL-6 was correlated with the risk of EH in the population assessed and we found the differences of IL-6 promoter methylation in gender, smoking and drinking.
authors.affiliation: Department of Preventive Medicine, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, China.
authors.forename: S-Q
authors.initials: SQ
authors.lastname: Mao
authors.affiliation: Department of Clinical Medicine, School of Medicine, Hang Zhou Normal University, Hangzhou, China.
authors.forename: J-H
authors.initials: JH
authors.lastname: Sun
authors.affiliation: Department of Preventive Medicine, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, China.
authors.forename: T-L
authors.initials: TL
authors.lastname: Gu
authors.affiliation: Health and Family Planning Commission of Zhenhai District, Ningbo, Zhejiang, China.
authors.forename: F-B
authors.initials: FB
authors.lastname: Zhu
authors.affiliation: Clinical Laboratory, The First Hospital of Ningbo, Zhejiang, China.
authors.forename: F-Y
authors.initials: FY
authors.lastname: Yin
authors.affiliation: Department of Preventive Medicine, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, China.
authors.forename: L-N
authors.initials: LN
authors.lastname: Zhang
mesh_terms: D000367:Age Factors; D000428:Alcohol Drinking / Q000009:adverse effects; D019540:Area Under Curve; D001794:Blood Pressure / Q000235:genetics*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D000075222:Essential Hypertension / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D011401:Promoter Regions, Genetic; D012372:ROC Curve; D012307:Risk Factors; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6