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Associations of estradiol levels and genetic polymorphisms of inflammatory genes with the risk of ischemic stroke.

ABSTRACT: 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.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.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.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.

SUBMITTER: Hsieh YC

PROVIDER: S-EPMC5371181 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Associations of estradiol levels and genetic polymorphisms of inflammatory genes with the risk of ischemic stroke.

Hsieh Yi-Chen YC Hsieh Fang-I FI Chen Yih-Ru YR Hu Chaur-Jong CJ Jeng Jiann-Shing JS Tang Sung-Chun SC Chi Nai-Fang NF Lin Huey-Juan HJ Lien Li-Ming LM Peng Giia-Sheun GS Chiou Hung-Yi HY

Journal of biomedical science 20170328 1

<h4>Background</h4>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.<h4>Methods</h4>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 s ...[more]

PMID: 28351426

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Project description:Background and Purpose- Although exogenous hormone therapy (HT) use has been associated with increased risk of ischemic stroke in postmenopausal women, it remains unknown whether sex hormone levels contribute to ischemic stroke risk. We aimed to estimate associations between plasma sex hormone levels and ischemic stroke risk, by HT status, in a nested case-control study of postmenopausal women from the NHS (Nurses' Health Study). Methods- Women with confirmed incident ischemic stroke (n=419) were matched with controls (n=419) by age, HT use, and other factors. Plasma estradiol and testosterone levels were measured using liquid chromatography tandem mass spectrometry; SHBG (sex hormone-binding globulin) was assayed by electrochemiluminescence immunoassay. Associations of total and free estradiol and testosterone, the estradiol/testosterone ratio, and SHBG with ischemic stroke were estimated using conditional logistic regressions stratified by HT status with adjustment for matching and cardiovascular risk factors. Results- Current HT users had different hormone profiles from never/past users. No clear linear trends were observed between estradiol (total or free) levels or the estradiol/testosterone ratio and ischemic stroke risk among either current users (Ptrend>0.1) or never/past users (Ptrend>0.6). For both current and never/past users, the associations between some of the sex hormones and ischemic stroke differed by body mass index categories (Pinteraction≤0.04). For women with a body mass index <25 kg/m2, a higher estradiol/testosterone ratio was associated with significantly elevated ischemic stroke risk among current users (Ptrend=0.01), and higher levels of total and free estradiol were significantly associated with higher ischemic stroke risk among never/past users (Ptrend≤0.04). Testosterone and SHBG were not associated with ischemic stroke in either current or never/past users. Conclusions- Our findings do not support a role of sex hormone levels in mediating ischemic stroke risk among postmenopausal women. Replications in additional larger studies are required.

Dataset Information

Associations of estradiol levels and genetic polymorphisms of inflammatory genes with the risk of ischemic stroke.

Publications

Associations of estradiol levels and genetic polymorphisms of inflammatory genes with the risk of ischemic stroke.

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