Fan Rui, Wang Wei-Jie, Zhong Qi-Long, Duan Shi-Wei, Xu Xu-Ting, Hao Ling-Mei, Zhao Jing, Zhang Li-Na
Department of Preventive Medicine, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, P.R. China.
Department of General Medicine, Ningbo Baizhang Street Community Health Service Center, Ningbo, Zhejiang 315211, P.R. China.
Mol Med Rep. 2015 Aug;12(2):2390-4. doi: 10.3892/mmr.2015.3631. Epub 2015 Apr 16.
Essential hypertension (EH) is commonly accompanied by a dysfunction of glucose metabolism. Glucokinase (GCK) is a key enzyme involved in glucose metabolism. The aim of the present study was to investigate whether GCK gene-body methylation contributed to the risk of EH. A total of 47 patients with EH and 47 age-matched controls were recruited for methylation research in the current study. GCK gene-body methylation was measured using bisulphite pyrosequencing technology. DNA methylation levels were closely correlated among CpG1, CpG2 and CpG3 (r>0.70; P<0.001), in contrast with a weaker correlation between CpG4 and the preceding three CpGs (r<0.3 or r=1; P>0.05). Significantly lower CpG13 methylation (cases vs. controls, 49.13 ± 5.72 vs. 53.49 ± 7.53%; adjusted P=0.006) and significantly higher CpG4 methylation (cases vs. controls, 46.34 ± 6.48 vs. 34.74 ± 12.73%; adjusted P=0.002) were observed in patients with EH. The present study indicated that aberrant methylation of the GCK gene body was significantly associated with the risk of EH in the population assessed. The discrepancies between CpG1‑3 and CpG4 methylation may suggest distinct roles for each of them in the determination of the risk of EH.
原发性高血压（EH）常伴有糖代谢功能障碍。葡萄糖激酶（GCK）是参与糖代谢的关键酶。本研究的目的是调查GCK基因体甲基化是否会增加EH风险。本研究共招募了47例EH患者和47例年龄匹配的对照进行甲基化研究。采用亚硫酸氢盐焦磷酸测序技术检测GCK基因体甲基化。CpG1、CpG2和CpG3之间的DNA甲基化水平密切相关（r>0.70；P<0.001），相比之下，CpG4与前三个CpG之间的相关性较弱（r<0.3或r=1；P>0.05）。在EH患者中观察到CpG13甲基化显著降低（病例组与对照组，49.13±5.72%对53.49±7.53%；校正P=0.006），而CpG4甲基化显著升高（病例组与对照组，46.34±6.48%对34.74±12.73%；校正P=0.002）。本研究表明，在评估的人群中，GCK基因体的异常甲基化与EH风险显著相关。CpG1-3和CpG4甲基化之间的差异可能表明它们在确定EH风险中各自具有不同的作用。
