HTRA1 methylation in peripheral blood as a potential marker for the preclinical detection of stroke: a case–control study and a prospective nested case–control study
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Published:2022-12
Issue:1
Volume:14
Page:
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ISSN:1868-7075
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Container-title:Clinical Epigenetics
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language:en
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Short-container-title:Clin Epigenet
Author:
Liu Chunlan,Li Mengxia,Yin Qiming,Fan Yao,Shen Chong,Yang Rongxi
Abstract
Abstract
Background
Stroke is the leading cause of mortality in China. DNA methylation has essential roles in multiple diseases, but its association with stroke was barely studied. We hereby explored the association between blood-based HTRA serine protease 1 (HTRA1) methylation and the risk of stroke.
Results
The association was discovered in a hospital-based case–control study (cases/controls = 190:190) and further validated in a prospective nested case–control study including 139 cases who developed stroke within 2 years after recruitment and 144 matched stroke-free controls. We observed stroke-related altered HTRA1 methylation and expression in both case–control study and prospective study. This blood-based HTRA1 methylation was associated with stroke independently from the known risk factors and mostly affected the older population. The prospective results further showed that the altered HTRA1 methylation was detectable 2 years before the clinical determination of stroke and became more robust with increased discriminatory power for stroke along with time when combined with other known stroke-related variables [onset time ≤ 1 year: area under the curve (AUC) = 0.76].
Conclusions
In our study, altered HTRA1 methylation was associated with stroke at clinical and preclinical stages and thus may provide a potential biomarker in the blood for the risk evaluation and preclinical detection of stroke.
Funder
National Natural Science Foundation of China
Publisher
Springer Science and Business Media LLC
Subject
Genetics (clinical),Developmental Biology,Genetics,Molecular Biology
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