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 ≤ 3, 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 ≤ 3, 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 ≤ 3, 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/β-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)1α, 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.