LINE-1 Methylation is Associated with an Increased Risk of Ischemic Stroke in Men
Reuy-Tay Lin, Edward Hsi, Hsiu-Fen Lin, Yi-Chu Liao, Yung-Song Wang and Suh-Hang H. Juo
Affiliation: Department of Genome Medicine, Kaohsiung Medical University, 100 TzYou First Road, Kaohsiung 80708, Taiwan.
The level of global DNA methylation may be related to the cerebrovascular disease. The methylation level of
Long Interspersed Nucleotide Element 1 (LINE-1) can represent the global methylation level. We investigated the
association between the methylation levels of LINE-1 and ischemic stroke in Chinese. Two hundred and eighty patients of
ischemic stroke and 280 age- and sex-matched controls were enrolled. The mean percentage of three CpG sites of LINE-1
was calculated for each subject and was used for analysis. Twenty four samples were re-checked for reproducibility of the
methylation assay. Multivariate regression model was used to estimate the odds ratio of stroke risk for one percent change
of methylation. Sex-specific analysis was also conducted. Thirty-two cases and 11 controls did not pass the methylation
assay criteria, and were excluded from further analysis. The intra-class correlation has a coefficient of 0.97 for the
methylation assay. The stroke cases had a lower methylation level than controls (p=0.002), especially male subjects
(p=0.001). Sex-specific analysis showed that a decrease of 1% methylation level in men could increase a stroke risk by
1.2-fold after adjusting for other risk factors. LINE-1 methylation levels did not have a significant association with stroke
in women. The present study shows that a lower level of LINE-1 methylation was associated with a higher risk for
ischemic stroke in men, but methylation level in women did not affect the stroke risk. Our finding in Chinese is consistent
with a previous result based on elderly white men.
Keywords: DNA Methylation, LINE-1, Ischemic stroke.
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