基于DNA甲基化的端粒长度比基于定量聚合酶链反应的端粒长度与心血管疾病及长期死亡率的关联更强：来自1999 - 2002年美国国家健康与营养检查调查（NHANES）的证据。

DNA methylation-based telomere length is more strongly associated with cardiovascular disease and long-term mortality than quantitative polymerase chain reaction-based telomere length: evidence from the NHANES 1999-2002.

作者信息

Wang Qianhui, Gao Yuanfeng, Song Jie, Taiwaikuli Dilare, Ding Huanhuan, Yang Xinchun, Tang Baopeng, Zhou Xianhui

机构信息

Department of Cardiac Pacing and Electrophysiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China.

Department of Heart Center, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.

出版信息

Clin Epigenetics. 2024 Dec 4;16(1):177. doi: 10.1186/s13148-024-01795-8.

DOI:10.1186/s13148-024-01795-8

PMID:39633416

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11619434/

Abstract

BACKGROUND

Telomere length (TL) serves as a pivotal gauge of cellular aging, with shorter TL linked to various age-related ailments. Recently, a DNA methylation-based TL estimator, known as DNAmTL, has emerged as a novel TL measurement tool. Our current investigation scrutinized the correlation between DNAmTL and the risks of cardiovascular disease (CVD) and enduring mortality among middle-aged and elderly individuals.

METHODS

We enrolled a nationwide, population-based cohort of subjects from the National Health and Nutrition Examination Survey spanning 1999 to 2002, possessing data on both DNAmTL and quantitative polymerase chain reaction-based TL (qPCRTL). Logistic regression models and Cox proportional hazards models were employed to evaluate the associations of DNAmTL with CVD risk and mortality, respectively.

RESULTS

The cohort comprised 2532 participants, with a weighted CVD prevalence of 19.06%. Notably, each one-kilobase increase in DNAmTL was linked to a 53% diminished CVD risk [odds ratio (OR): 0.47, 95% confidence interval (CI): 0.23-0.95, P = 0.035]. Over a median follow-up period of 206 months, 1361 deaths were recorded (53.75%), with 590 (23.30%) ascribable to CVD. Individuals with the lengthiest DNAmTL exhibited a 36% lower risk of all-cause mortality (hazard ratio (HR): 0.64, 95% CI: 0.49-0.85, P = 0.002) and a 35% decrease in CVD mortality (HR: 0.65, 95% CI: 0.43-0.98, P = 0.044) compared to those with shortest DNAmTL. Notably, a stronger association with age was observed for DNAmTL compared to qPCRTL (r = -0.58 vs. r = - 0.25). Analysis of receiver operating characteristic (ROC) curves suggested superior predictive performance of DNAmTL over qPCRTL for CVD (area under curve (AUC): 0.63 vs. 0.55, P < 0.001), all-cause (AUC: 0.74 vs. 0.62, P < 0.001), and CVD mortality (AUC: 0.75 vs. 0.64, P < 0.001).

CONCLUSION

Longer DNAmTL was positively correlated with reduced CVD risk and long-term mortality in middle-aged and elderly cohorts. Notably, DNAmTL outperformed qPCRTL as an aging biomarker in the stratification of CVD risks and mortality.

摘要

背景

端粒长度（TL）是细胞衰老的关键指标，较短的TL与各种年龄相关疾病有关。最近，一种基于DNA甲基化的TL估计器，即DNAmTL，已成为一种新型的TL测量工具。我们目前的研究审视了DNAmTL与心血管疾病（CVD）风险以及中老年人群持久死亡率之间的相关性。

方法

我们纳入了一个来自1999年至2002年全国健康与营养检查调查的全国性、基于人群的队列研究对象，他们同时拥有DNAmTL和基于定量聚合酶链反应的TL（qPCRTL）数据。采用逻辑回归模型和Cox比例风险模型分别评估DNAmTL与CVD风险和死亡率的关联。

结果

该队列包括2532名参与者，加权CVD患病率为19.06%。值得注意的是，DNAmTL每增加1千碱基，CVD风险降低53%[优势比（OR）：0.47，95%置信区间（CI）：0.23 - 0.95，P = 0.035]。在中位随访期206个月内，记录了1361例死亡（53.75%），其中590例（23.30%）归因于CVD。与DNAmTL最短的个体相比，DNAmTL最长的个体全因死亡率风险降低36%（风险比（HR）：0.64，95% CI：0.49 - 0.85，P = 0.002），CVD死亡率降低35%（HR：0.65，95% CI：0.43 - 0.98，P = 0.044）。值得注意的是，与qPCRTL相比，观察到DNAmTL与年龄的关联更强（r = -0.58对r = -0.25）。受试者工作特征（ROC）曲线分析表明，在预测CVD（曲线下面积（AUC）：0.63对0.55，P < 0.001）、全因（AUC：0.74对0.62，P < 0.001）和CVD死亡率方面，DNAmTL的预测性能优于qPCRTL（AUC：0.75对0.64，P < 0.001）。