Abstract
BackgroundEstrogen plays an important role as an anti-inflammatory and neuroprotective agent in ischemic stroke. In this study, we analyzed the effect of a polygenic risk score (PRS) constructed using inflammatory genes and estradiol levels on the risk of ischemic stroke.MethodsThis case-control study was conducted with 624 ischemic stroke patients and 624 age- and gender-matched controls. The PRS estimated the polygenic contribution of inflammatory genes from ischemic stroke susceptibility loci. Estradiol levels were measured using a radioimmunoassay. High and low estradiol levels were defined according to the log-transformed median estradiol levels in female and male controls.ResultsSubjects in the fourth quartile of the PRS had a significant 1.57-fold risk of ischemic stroke (95% confidence interval [CI], 1.12 ~ 2.19), after adjusting for covariates compared to individuals in the lowest quartile. Compared to individuals with high estradiol levels and a low PRS as the reference group, those exposed to low estradiol levels and a high PRS had an increased risk of ischemic stroke (odds ratio, 3.35; 95% CI, 1.79 ~ 6.28). Similar results were also observed in males when the analysis was stratified by gender.ConclusionsOur data suggest that the PRS can be useful in evaluating a high risk of ischemic stroke among patients, especially those exposed to low estradiol levels.
Highlights
Estrogen plays an important role as an anti-inflammatory and neuroprotective agent in ischemic stroke
Ischemic stroke was defined as a focal neurologic deficit of presumed vascular cause with sudden onset and lasting for at least 24 h as a recent infarct in a clinically relevant area of the brain on a computed tomographic (CT) or magnetic resonance imaging (MRI) brain scan performed within 10 days of the event
The frequencies of either one or both cigarette smoking/alcohol consumption habits were significantly higher in patients than in controls
Summary
Estrogen plays an important role as an anti-inflammatory and neuroprotective agent in ischemic stroke. We analyzed the effect of a polygenic risk score (PRS) constructed using inflammatory genes and estradiol levels on the risk of ischemic stroke. Neuroinflammation is a general process of several neurodegenerative diseases and may play an important role in the pathogenesis of ischemic stroke [1]. Several studies showed that decreases in estrogen-induced vascular inflammatory markers, including cytokines and adhesion molecules, might be the mechanism of vascular protection [13, 14]. A novel and unique mechanism for the antiinflammatory activity of 17β-estradiol (E2) was found, which indicated that E2 prevents inflammatory gene transcription induced by inflammatory agents by inhibiting NF-κB intracellular transport [15, 16]
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