AUTHOR=Liu Chunlan , Yin Qiming , Li Mengxia , Fan Yao , Shen Chong , Yang Rongxi 

TITLE=ACTB Methylation in Blood as a Potential Marker for the Pre-clinical Detection of Stroke: A Prospective Nested Case-Control Study

JOURNAL=Frontiers in Neuroscience

VOLUME=15

YEAR=2021

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2021.644943

DOI=10.3389/fnins.2021.644943

ISSN=1662-453X

ABSTRACT=<sec><title>Background</title><p>Stroke is the second leading cause of death worldwide. If risk of stroke could be evaluated early or even at a preclinical stage, the mortality rate could be reduced dramatically. However, the identified genetic factors only account for 5–10% of the risk of stroke. Studies on the risk factors of stroke are urgently needed. We investigated the correlation between blood-based β-actin (<italic>ACTB</italic>) methylation and the risk of stroke in a prospective nested case-control study.</p></sec><sec><title>Methods</title><p>The methylation level of <italic>ACTB</italic> was quantitatively determined by mass spectrometry in 139 stroke cases who developed stroke within 2 years after recruitment and 147 age- and sex-matched controls who remained stroke-free in a median follow-up of 2.71 years.</p></sec><sec><title>Results</title><p>We observed a highly significant correlation between hypomethylation of one CpG site of <italic>ACTB</italic> and increased risk of stroke in an onset-time-dependent manner (for onset time ≤ 1.5 years: odds ratio (OR) per + 10% methylation = 0.76, <italic>P</italic> = 0.001; for onset time ≤ 1.32 years: OR per + 10% methylation = 0.59, <italic>P</italic> = 7.82 × 10<sup>–7</sup>; for onset time ≤ 1 year: OR per + 10% methylation = 0.43, <italic>P</italic> = 3.00 × 10<sup>–6</sup>), and the increased cumulative incidence of stroke (log-rank <italic>P</italic> = 3.13 × 10<sup>–7</sup>). Neighboring CpG sites showed an inverse correlation with age and drinking status in controls (<italic>P</italic> &lt; 0.05) but not in stroke cases.</p></sec><sec><title>Conclusion</title><p>We firstly reported the blood-based <italic>ACTB</italic> methylation as a marker for the risk evaluation and preclinical detection of stroke, which can be further modified by age and drinking.</p></sec>