Abstract

Background: Estrogen 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. Methods: This 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. Results: Subjects 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. Conclusions: Our 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.

Original languageEnglish
Article number25
JournalJournal of Biomedical Science
Volume24
Issue number1
DOIs
Publication statusPublished - Mar 28 2017

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Genetic Polymorphisms
Polymorphism
Estradiol
Genes
Stroke
Confidence Intervals
Neuroprotective Agents
Radioimmunoassay
Case-Control Studies
Estrogens
Anti-Inflammatory Agents
Odds Ratio

Keywords

  • Estradiol
  • Inflammation
  • Ischemic stroke
  • Polygenic risk score

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology
  • Biochemistry, medical
  • Pharmacology (medical)

Cite this

Associations of estradiol levels and genetic polymorphisms of inflammatory genes with the risk of ischemic stroke. / Hsieh, Yi Chen; Hsieh, Fang I.; Chen, Yih Ru; Hu, Chaur Jong; Jeng, Jiann Shing; Tang, Sung Chun; Chi, Nai Fang; Lin, Huey Juan; Lien, Li Ming; Peng, Giia Sheun; Chiou, Hung Yi.

In: Journal of Biomedical Science, Vol. 24, No. 1, 25, 28.03.2017.

Research output: Contribution to journalArticle

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abstract = "Background: Estrogen 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. Methods: This 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. Results: Subjects 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. Conclusions: Our 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.",
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author = "Hsieh, {Yi Chen} and Hsieh, {Fang I.} and Chen, {Yih Ru} and Hu, {Chaur Jong} and Jeng, {Jiann Shing} and Tang, {Sung Chun} and Chi, {Nai Fang} and Lin, {Huey Juan} and Lien, {Li Ming} and Peng, {Giia Sheun} and Chiou, {Hung Yi}",
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AU - Hsieh, Yi Chen

AU - Hsieh, Fang I.

AU - Chen, Yih Ru

AU - Hu, Chaur Jong

AU - Jeng, Jiann Shing

AU - Tang, Sung Chun

AU - Chi, Nai Fang

AU - Lin, Huey Juan

AU - Lien, Li Ming

AU - Peng, Giia Sheun

AU - Chiou, Hung Yi

PY - 2017/3/28

Y1 - 2017/3/28

N2 - Background: Estrogen 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. Methods: This 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. Results: Subjects 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. Conclusions: Our 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.

AB - Background: Estrogen 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. Methods: This 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. Results: Subjects 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. Conclusions: Our 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.

KW - Estradiol

KW - Inflammation

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KW - Polygenic risk score

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