Effects of Gender on Gene Expression in the Blood of Ischemic Stroke Patients

Abstract

This study examined the effects of gender on RNA expression after ischemic stroke (IS). RNA obtained from blood of IS patients (n = 51; 153 samples at p3, 5, and 24 hours) and from matched controls (n = 52) were processed on Affymetrix microarrays. Analyses of covariance for stroke versus control samples were performed separately for both genders and the regulated genes for females compared with males. In all, 242, 227, and 338 male-specific genes were regulated at p3, 5, and 24 hours after IS, respectively, of which 59 were regulated at all time points. Overall, 774, 3,437, and 571 female-specific stroke genes were regulated at p3, 5, and 24 hours, respectively, of which 152 were regulated at all time points. Male-specific stroke genes were associated with integrin, integrin-liked kinase, actin, tight junction, Wnt/b-catenin, RhoA, fibroblast growth factors (FGF), granzyme, and tumor necrosis factor receptor (TNFR)2 signaling. Female-specific stroke genes were associated with p53, high-mobility group box-1, hypoxia inducible factor (HIF)1a, interleukin (IL)1, IL6, IL12, IL18, acute-phase response, T-helper, macrophage, and estrogen signaling. Cell death signaling was overrepresented in both genders, although the molecules and pathways differed. Gender affects gene expression in the blood of IS patients, which likely implies gender differences in immune, inflammatory, and cell death responses to stroke.

Blood transcriptome changes after stroke in an African American population

“…obs. Robert Meller RM), which agrees with reports of gene expression differences following stroke between males and females 28, 29. These preliminary data show the clear need for further studies to better understand both racial and sex‐associated differences in response to stroke.…”

Impact of Sex Difference on Severity and Functional Outcome in Patients with Cardioembolic Stroke

“…12 Recent studies further showed that there are sex-associated changes in gene expressions in the blood obtained from patients with ischemic stroke 13 and in microRNA expression in mice with cerebral ischemia. 14 These sex-associated responses to cerebral ischemia may partly contribute to sex difference in stroke severity.…”

Expression profile based gene clusters for ischemic stroke detection

“…Results from Oh et al[21] were published after this study commenced. In several other microarray studies the utility of gene expression was investigated: for the evaluation of the risk of hemorrhagic transformation[23], defining stroke etiology[24-26] and in studying gender related gene expression changes in stroke patients[27,28]. …”