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.
Keywords: DNA Methylation, LINE-1, Ischemic stroke.
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.
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