天津医药

天津医药 ›› 2025, Vol. 53 ›› Issue (9): 987-992.doi: 10.11958/20251552

• 应用研究 • 上一篇    下一篇

Furin启动子甲基化水平与社区非糖尿病人群血压的相关性

贾薇1(), 田志2,△()   

  1. 1 吉首大学医学院生理教研室（邮编416000）
    2 吉首大学附属第一医院神经外科
  • 收稿日期:2025-04-17 修回日期:2025-05-26 出版日期:2025-09-15 发布日期:2025-09-16
  • 通讯作者: △E-mail：tztz17@163.com
  • 作者简介:贾薇（1981），女，讲师，主要从事脑血管疾病及脑肿瘤的血管相关机制方面研究。E-mail：jiaweiwei100@126.com
  • 基金资助:
    湖南省卫生适宜技术推广项目(202218015878);湖南省卫生健康高层次人才重大科研专项项目(R2023172)

Correlation between Furin promoter methylation levels and blood pressure of non-diabetic population in a community

JIA Wei1(), TIAN Zhi2,△()   

  1. 1 Department of Physiology, School of Medicine, Jishou University, Jishou 416000, China
    2 Department of Neurosurgery, the First Affiliated Hospital of Jishou University
  • Received:2025-04-17 Revised:2025-05-26 Published:2025-09-15 Online:2025-09-16
  • Contact: △E-mail: tztz17@163.com

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摘要：

目的 探讨Furin基因启动子甲基化水平与社区非糖尿病人群血压的相关性。方法 对Dryad开放数据库中一项关于Furin启动子甲基化率与糖尿病发生风险的研究数据进行二次分析。纳入原数据的参与者后，排除既往有心血管疾病史、糖尿病病史或者入组时检测出糖尿病、缺乏血液样本、拒绝随访、随访期间死亡、数据缺失的参与者后，最终1 832例研究对象组成社区非糖尿病人群。收集该人群基线时的Furin启动子区8个CpG位点的甲基化率、空腹血糖、血压、血脂。根据收缩压（SBP）是否≥140 mmHg（1 mmHg=0.133 kPa）、舒张压（DBP）是否≥90 mmHg，以及高血压判定标准（SBP≥140 mmHg或DBP≥90 mmHg）将研究对象分为SBP正常组（1 388例）和SBP升高组（444例）；DBP正常组（1 341例）和DBP升高组（491例）；血压正常组（1 218例）和高血压组（614例）。采用多因素线性回归模型观察Furin启动子甲基化率分别与SBP和DBP相关性。针对SBP/DBP独立相关的Furin启动子甲基化位点，通过调整混杂因素后的线性回归模型拟合曲线观察SBP/DBP与Furin启动子甲基化率是否存在非线性关系；采用未调整和调整的Logistic回归模型观察Furin启动子甲基化率与高血压风险的相关性；调整的Logistic回归模型的调整因素与线性回归拟合曲线的调整因素相同。结果 与SBP正常组比较，SBP升高组CpG1、CpG2和CpG4甲基化率降低，而CpG8甲基化率升高（P<0.05）；与DBP正常组比较，DBP升高组CpG2、CpG4甲基化率降低，CpG8甲基化率升高（P<0.01）；与血压正常组比较，高血压组CpG1、CpG2、CpG4、CpG6甲基化率降低，CpG8甲基化率升高（P<0.05）。多因素线性回归分析显示，CpG2位点甲基化率下降以及CpG8位点的甲基化率升高与SBP和DBP升高均独立相关。线性回归模型拟合曲线显示，CpG2位点甲基化率升高与SBP和DBP的下降均呈线性关系（P for non-linearity分别为0.143和0.481），CpG8位点甲基化率升高与SBP和DBP的升高也均呈现线性关系（P for non-linearity分别为0.727和0.940）。未调整模型的Logistic回归结果显示CpG2和CpG8甲基化率是高血压的相关因素（P<0.01）。调整模型的Logistic回归结果显示CpG2甲基化率升高是高血压的独立保护因素，CpG8甲基化率升高是高血压的独立危险因素（P<0.01）。结论 Furin启动子CpG2和CpG8位点甲基化水平是社区非糖尿病人群血压的独立相关因素。

关键词: 高血压, 费林蛋白酶, 启动区, 遗传, 甲基化, 非糖尿病

Abstract:

Objective To investigate the correlation between Furin promoter methylation level and blood pressure in a community-based non-diabetic population. Methods A secondary analysis was conducted on the research data from a study in the Dryad open database regarding the methylation rate of Furin promoter and the risk of diabetes. After including the participants from the original data and excluding those with a history of cardiovascular disease, diabetes or diagnosed diabetes at the time of enrollment, those lacking blood samples, those who refused to participate in follow-up examinations, those who died during the follow-up period and those with missing data, a total of 1 832 subjects formed the community non-diabetic population. The methylation rates of 8 CpG sites in the Furin promoter region, fasting blood glucose, lipid and blood pressure were collected at baseline. The subjects were divided into the normal systolic blood pressure (SBP) group (1 388 cases) and the elevated SBP group (444 cases) based on whether SBP was ≥140 mmHg, the diastolic blood pressure (DBP) was ≥90 mmHg and the hypertension diagnostic criteria (SBP≥140 mmHg or DBP≥90 mmHg. There were 1 341 cases in the normal DBP group, 491 cases in the elevated DBP group and 1 218 cases in the normal blood pressure group. A multivariate linear regression model was used to observe the correlation between the methylation rate of the Furin promoter and changes of SBP and DBP. For the Furin promoter methylation sites independently related to SBP/DBP. Linear regression models adjusted for confounding factors were used to fit the curve to observe whether there was a non-linear relationship between SBP or DBP and the methylation rate of the Furin promoter, respectively. Unadjusted and adjusted Logistic regression models were used to observe the correlation between the methylation rate of the Furin promoter and the risk of hypertension. The adjustment factors in the adjusted Logistic regression model were identical to those in the linear regression fitting curve. Results Compared with the normal SBP group, the methylation rates of CpG1, CpG2 and CpG4 were decreased in the elevated SBP group, while the methylation rate of CpG8 was increased (P<0.05). Compared with the normal DBP group, the methylation rates of CpG2 and CpG4 were decreased in the elevated DBP group, while the methylation rate of CpG8 was increased (P<0.01). Compared with the normal blood pressure group, the methylation rates of CpG1, CpG2, CpG4 and CpG6 were decreased in the hypertension group, while the methylation rate of CpG8 was increased (P<0.05). Multivariate linear regression analysis showed that the decreased methylation rate at the CpG2 site and the increased methylation rate at the CpG8 site were independently associated with elevated SBP and DBP. The linear regression model fitting curves indicated that the increased methylation rate at the CpG2 site was linearly related to the decrease in SBP/DBP (P values for non-linearity were 0.143 and 0.481, respectively), and the increased methylation rate at the CpG8 site was linearly related to the increase in SBP/DBP (P values for non-linearity were 0.727 and 0.940, respectively). Unadjusted Logistic regression analysis showed that the methylation rates of CpG2 and CpG8 were influencing factors of hypertension (P<0.01). Adjusted Logistic regression analysis showed that the increased methylation rate at the CpG2 site was independent protective factors, and the increased methylation rate at the CpG8 site was independent risk factor for hypertension (P<0.01). Conclusion The methylation levels at the CpG2 and CpG8 sites of the Furin promoter are independent factors associated with blood pressure changes in the non - diabetic population in the community.

Key words: hypertension, Furin, promoter regions, genetic, methylation, non-diabetes

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