Mao S-Q, Sun J-H, Gu T-L, Zhu F-B, Yin F-Y, Zhang L-N
Department of Preventive Medicine, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, China.
Department of Clinical Medicine, School of Medicine, Hang Zhou Normal University, Hangzhou, China.
J Hum Hypertens. 2017 Aug;31(8):530-536. doi: 10.1038/jhh.2017.7. Epub 2017 Mar 16.
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.
原发性高血压（EH）是一种具有明确表观遗传成分的慢性疾病。炎症和内皮功能障碍在持续性血压升高的发展过程中起重要作用。本研究的目的是探讨在炎症过程中EH与促炎细胞因子基因白细胞介素-6（IL-6）的DNA甲基化之间的关联。我们使用亚硫酸氢盐焦磷酸测序技术对96例EH患者和96例年龄及性别匹配的健康对照者的外周血DNA进行了甲基化分析。目前的结果显示，与对照组相比，EH组中IL-6启动子CpG岛的三个胞嘧啶-磷酸-鸟嘌呤（CpG）位点甲基化程度较低，但只有CpG2（58.43±7.53对62.34±9.65，P=0.004）和CpG3（51.52±6.18对57.45±8.29，P<0.001）有统计学差异。逻辑回归分析发现CpG3低甲基化是EH的一个危险因素（比值比=1.111，校正P=0.004）。此外，我们发现男性中CpG1（64.84±7.06对61.84±8.61）和CpG2（62.04±7.40对59.30±9.57）的甲基化程度高于女性。在男性中，我们发现吸烟者与非吸烟者相比，CpG2（60.41±7.74对64.28±6.36）和CpG3（53.70±8.62对57.78±7.87）低甲基化，饮酒者与非饮酒者相比，CpG2（60.89±7.32对64.70±7.03）和CpG3（53.23±7.99对60.48±7.58）低甲基化。此外，CpG2和CpG3与收缩压和舒张压呈负相关（P<0.05）。受试者工作特征曲线分析显示，CpG2（曲线下面积：0.638，P=0.001）和CpG3（曲线下面积：0.704，P<0.001）对预测EH风险具有诊断价值。总之，我们的研究揭示了IL-6的低甲基化与所评估人群中EH的风险相关，并且我们发现了IL-6启动子甲基化在性别、吸烟和饮酒方面的差异。
