Bao Xing-Jie, Mao Shu-Qi, Gu Tian-Lun, Zheng Shu-Ying, Zhao Jin-Shun, Zhang Li-Na
Department of Preventive Medicine, Zhejiang Provincial Key Laboratory of Pathological and Physiological Technology, Medical School of Ningbo University.
Beilun District Center for Disease Control and Prevention.
Tohoku J Exp Med. 2018 Apr;244(4):283-290. doi: 10.1620/tjem.244.283.
Essential hypertension (EH) is a multifactorial disease. Interferon-γ (IFN-γ) plays an important role in the onset of EH through cytokine-mediated systemic inflammatory responses. We aimed to determine whether the methylation status of the IFN-γ gene (IFNG) promoter is involved in the pathogenesis of EH. Six copies of CpG dinucleotides are distributed between 3,203 bp and 3,121 bp upstream from the transcription initiation site of IFNG, termed CpG1 to CpG6 in the 5'-to-3' direction. We recruited 96 patients with EH and 96 sex- and age-matched healthy subjects as controls. Using bisulfate pyrosequencing datasets, we analyzed the methylation status of the six CpG sites and thus found that CpG5 was consistently methylated in all of the 96 EH patients and 96 control subjects. Among the remaining five CpG sites, there was no significant difference in the methylation levels of CpG4 and CpG6 between the two groups. By contrast, CpG1 (P = 0.003) and CpG3 (P = 5.87 × 10) were highly methylated among the EH subjects compared with the controls, whereas CpG2 (P = 1.24 × 10) was significantly less methylated in among EH subjects. The methylation levels of CpG2 were still lower after adjustment with logistic regression (adjusted P = 0.032). The CpG2 methylation level was an effective marker of EH (area under curve = 0.384; P = 1.40 × 10). The present study shows that hypomethylation of the IFNG promoter is significantly related to the risk of EH, providing new insights into the pathogenesis of EH.
原发性高血压（EH）是一种多因素疾病。干扰素-γ（IFN-γ）通过细胞因子介导的全身炎症反应在EH的发病机制中起重要作用。我们旨在确定IFN-γ基因（IFNG）启动子的甲基化状态是否参与EH的发病机制。六个CpG二核苷酸拷贝分布在IFNG转录起始位点上游3203 bp至3121 bp之间，从5'到3'方向称为CpG1至CpG6。我们招募了96例EH患者和96例性别和年龄匹配的健康受试者作为对照。使用亚硫酸氢盐焦磷酸测序数据集，我们分析了六个CpG位点的甲基化状态，结果发现96例EH患者和96例对照受试者中CpG5均持续甲基化。在其余五个CpG位点中，两组之间CpG4和CpG6的甲基化水平无显著差异。相比之下，与对照组相比，EH受试者中CpG1（P = 0.003）和CpG3（P = 5.87×10）高度甲基化，而EH受试者中CpG2（P = 1.24×10）甲基化程度明显较低。经逻辑回归调整后，CpG2的甲基化水平仍然较低（调整后P = 0.032）。CpG2甲基化水平是EH的有效标志物（曲线下面积 = 0.384；P = 1.40×10）。本研究表明，IFNG启动子的低甲基化与EH风险显著相关，为EH的发病机制提供了新的见解。
