Abstract
Genetic factors play an important role in the pathogenesis of ischemic stroke. Of these, epigenetic modifications provide a new direction for the study of ischemic stroke pathogenesis. This study aimed to determine the correlation between DNA methylation of the gene encoding S-adenosylhomocysteine hydrolase (AHCY) and the risk of ischemic stroke in 64 ischemic stroke patients and 138 patients with traumatic brain injury (control group). The methylation level of AHCY was analyzed using quantitative methylation-specific polymerase chain reaction. Statistically significant differences in AHCY methylation levels were observed between the case group [medians (interquartile range): 0.13% (0.09%, 0.27%)] and the control group [0.06% (0.00%, 0.17%), p < 0.0001], and these associations remained significant in both male (p = 0.003) and female (p = 0.0005) subjects. A subgroup analysis by age revealed a considerably higher percentage of methylated AHCY in the case group than the control group in all age groups (age < 60 years, p = 0.007; age ≥ 60 years, p < 0.0001). A receiver operating characteristic (ROC) curve analysis revealed a trend toward a role for AHCY methylation as an indicator of risk in all ischemic patients [area under the curve (AUC) = 0.70, p = 0.0001], male patients (AUC = 0.67, p = 0.004), and female patients (AUC = 0.75, p = 0.0002). Our study confirmed a significant association between the AHCY DNA methylation level and the risk of ischemic stroke, suggesting that this gene methylation pattern may be a potential diagnostic marker of ischemic stroke.
Highlights
Stroke is among the three leading causes of disease-related mortality in humans and a common cause of chronic disability in adults [1], and poses a serious risk to human health and places a heavy burden on society [2]
As the homocysteine level is considered an independent predictor of severe neurological impairment in ischemic stroke patients, we hypothesized that DNA methylation of adenosylhomocysteine hydrolase (AHCY) may play a key role in the pathological development of ischemic stroke. In this case-control study, we explored the role of DNA methylation of AHCY as a risk factor for ischemic stroke in a Chinese population
No significant differences were observed with respect to the other demographic and clinical characteristics between the two groups
Summary
Stroke is among the three leading causes of disease-related mortality in humans and a common cause of chronic disability in adults [1], and poses a serious risk to human health and places a heavy burden on society [2]. Stroke can be divided etiologically as ischemic or hemorrhagic stroke [3]. Regarding the former type, common risk factors such as diabetes, hypertension, and hyperlipidemia can explain only a small fraction of the actual risk [4]. Studies have shown that genetic factors play key roles in the pathogenesis of ischemic stroke [5,6]. Submitted: 27 November 2019/Accepted: 30 December 2019
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