外周血PON1基因高甲基化、端粒长度变短与脑梗死发病相关
| 作者: |
1肖健豪,
1袁倩,
1张斯淼,
2李晓东,
3段世伟,
1,4王运良
1 郑州大学第二附属医院神经内科，郑州 450014 2 郑州大学附属郑州中心医院神经内科，郑州 450000 3 宁波大学医学院，浙江省病理生理学技术研究重点实验室，浙江 宁波 315211 4 解放军第960医院淄博院区神经内科，山东 淄博 255330 |
| 通讯: |
段世伟
Email: duanshiwei@nbu.edu.cn 王运良 Email: wangyunliang81@163.com |
| DOI: | 10.3978/j.issn.2095-6959.2019.05.015 |
| 基金: | 河南省卫生与计划生育委员会科技创新型人才“51282”工程基金 [ 豫卫科 (2016)32 号 ]；宁波大学王宽诚幸福基金 [ 宁大政 (2000)194 号 ]。 |
摘要
目的：探讨对氧磷酶1(paraoxonase1，PON1)基因启动子区甲基化水平和端粒长度与中国山东地区汉族人群脑梗死发病的相关性。方法：选取152例确诊脑梗死患者为病例组，152例健康人为对照组，提取外周静脉血基因组DNA，使用荧光定量甲基化特异性PCR(quantitative methylation-specific PCR，qMSP)测定受试者的血液PON1基因启动子甲基化水平及端粒长度。每个样本的甲基化程度以甲基化参考百分比(PMR)来表示。结果：病例组中PON1甲基化程度显著高于对照组(Z=−3.898，P=0.0001)，性别亚组显示差异主要在男性中更为显著(Z=−3.786，P=0.0002)。病例组患者的端粒长度显著低于对照组(Z=−11.843，P<0.0001)，且男女亚组中端粒长度均显著低于对照组(P<0.05)。然而，并没有发现PON1甲基化水平与端粒长度的相关性(病例组r=0.023，P=0.775；对照组r=−0.157，P=0.054)。结论：PON1启动子区高甲基化和端粒长度变短与脑梗死发病相关，是中国山东地区汉族人群脑梗死发病的危险因素。
关键词：
脑梗死；DNA甲基化；端粒长度；PON1
Hypermethylation of PON1 gene and shortening of telomere length in peripheral blood are associated with cerebral infarction
CorrespondingAuthor: DUAN Shiwei Email: duanshiwei@nbu.edu.cn
DOI: 10.3978/j.issn.2095-6959.2019.05.015
Foundation: This work was supported by the “51282” Project of Health and Family Planning Commission of Henan Province [(2016) 32] and the KC Wong Magna Fund in Ningbo University [(2000) 194], China.
Abstract
Objective: To investigate the correlation between methylation level of promoter region of PON1 gene, telomere length and cerebral infarction in Shandong Han population of China. Methods: A total of 152 patients with cerebral infarction were assigned to a case group and 152 healthy subjects served as a control group. The quantitative methylation-specific PCR (qMSP) was used to determine the promoter methylation level of PON1 gene and detection of telomere length. The methylation level was expressed as a methylation reference percentage (PMR). Results: The level of PON1 methylation in the case group was significantly higher than that in the control group (Z=−3.898, P=0.0001), gender subgroup showed that the difference was more significant in males (Z=−3.786, P=0.0002). Telomere length in the case group was significantly lower than that in the control group (Z=−11.843, P<0.0001), telomere length in male and female subgroups was both significantly lower than that in control group (P<0.05). However, there was no correlation between PON1 methylation level and telomere length (the case group: r=0.023, P=0.775; the control group: r=−0.157, P=0.054). Conclusion: Hypermethylation of PON1 promoter region and shorter telomere length are associated with cerebral infarction and are the risk factors of cerebral infarction in Han population in Shandong area of China.
Keywords：
cerebral infarction; DNA methylation; telomere length; PON1