title: Associations of estradiol levels and genetic polymorphisms of inflammatory genes with the risk of ischemic stroke.
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.
authors.affiliation: Program for Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan. ychsieh@tmu.edu.tw.|Center for Neurotrauma and Neuroregeneration, Taipei Medical University, Taipei, Taiwan. ychsieh@tmu.edu.tw.|Program in Biotechnology Research and Development, College of Pharmacy, Taipei Medical University, Taipe, Taiwan. ychsieh@tmu.edu.tw.
authors.forename: Yi-Chen
authors.initials: YC
authors.lastname: Hsieh
authors.affiliation: School of Public Health, College of Public Health, Taipei Medical University, Taipei, Taiwan.
authors.forename: Fang-I
authors.initials: FI
authors.lastname: Hsieh
authors.affiliation: School of Public Health, College of Public Health, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yih-Ru
authors.initials: YR
authors.lastname: Chen
authors.affiliation: Department of Neurology, Taipei Medical University Shuang Ho Hospital, New Taipei City, Taiwan.|Department of Neurology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.|Cerebrovascular Research Center, Taipei Medical University, Taipei, Taiwan.
authors.forename: Chaur-Jong
authors.initials: CJ
authors.lastname: Hu
authors.affiliation: Stroke Center and Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Jiann-Shing
authors.initials: JS
authors.lastname: Jeng
authors.affiliation: Stroke Center and Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Sung-Chun
authors.initials: SC
authors.lastname: Tang
authors.affiliation: Department of Neurology, Taipei Medical University Shuang Ho Hospital, New Taipei City, Taiwan.|Department of Neurology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.|Cerebrovascular Research Center, Taipei Medical University, Taipei, Taiwan.
authors.forename: Nai-Fang
authors.initials: NF
authors.lastname: Chi
authors.affiliation: Department of Emergency Medicine, Chi-Mei Medical Center, Tainan, Taiwan.|Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan.
authors.forename: Huey-Juan
authors.initials: HJ
authors.lastname: Lin
authors.affiliation: Department of Neurology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.|School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Li-Ming
authors.initials: LM
authors.lastname: Lien
authors.affiliation: Division of Neurology, Department of Internal Medicine, Taipei Veterans General Hospital, Hsinchu Branch, Hsinchu County, Taiwan.
authors.forename: Giia-Sheun
authors.initials: GS
authors.lastname: Peng
authors.affiliation: School of Public Health, College of Public Health, Taipei Medical University, Taipei, Taiwan. hychiou@tmu.edu.tw.
authors.forename: Hung-Yi
authors.initials: HY
authors.lastname: Chiou
mesh_terms: D000368:Aged; D002545:Brain Ischemia / Q000235:genetics*; D016022:Case-Control Studies; D004958:Estradiol / Q000378:metabolism*; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020412:Multifactorial Inheritance; D011110:Polymorphism, Genetic; D012307:Risk Factors; D020521:Stroke / Q000235:genetics*
chemical_list: D004967:Estrogens; D004958:Estradiol
keywords: Estradiol; Inflammation; Ischemic stroke; Polygenic risk score