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.
{"title":"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.","authors":"Qianhui Wang, Yuanfeng Gao, Jie Song, Dilare Taiwaikuli, Huanhuan Ding, Xinchun Yang, Baopeng Tang, Xianhui Zhou","doi":"10.1186/s13148-024-01795-8","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"16 1","pages":"177"},"PeriodicalIF":4.8000,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11619434/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical Epigenetics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s13148-024-01795-8","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 0
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.
期刊介绍:
Clinical Epigenetics, the official journal of the Clinical Epigenetics Society, is an open access, peer-reviewed journal that encompasses all aspects of epigenetic principles and mechanisms in relation to human disease, diagnosis and therapy. Clinical trials and research in disease model organisms are particularly welcome.